CN105126077A - Application of chlamydia protein Pgp3 in preparation of drugs for restraining psoriasis-like lesions - Google Patents
Application of chlamydia protein Pgp3 in preparation of drugs for restraining psoriasis-like lesions Download PDFInfo
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- CN105126077A CN105126077A CN201510634943.4A CN201510634943A CN105126077A CN 105126077 A CN105126077 A CN 105126077A CN 201510634943 A CN201510634943 A CN 201510634943A CN 105126077 A CN105126077 A CN 105126077A
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- Peptides Or Proteins (AREA)
Abstract
The invention discloses the application of chlamydia protein Pgp3 in preparation of drugs for restraining psoriasis-like lesions and belongs to the field of microorganisms and enzymes. The chlamydia protein Pgp3 can be combined with human antimicrobial peptide LL-37 to restrain the development of psoriasis-like lesions. The problems of existing drugs for treating psoriasis that side effect is serious, the physical safety of a patient and the effectiveness of the drugs can not be guaranteed after long-term use, and treatment cost is high are effectively solved. The chlamydia protein comes from chlamydia trachomatis, has a less serious side effect and a remarkable treatment effect compared with chemical drugs, and is expected to replace currently used psoriasis treatment drugs which are external-use hormone mostly.
Description
Technical field
The invention belongs to microorganism and enzyme field, specifically a kind of I (chlamydia) protein Pgp3 suppresses the application in Pigs with Psoriasis medicine in preparation.
Background technology
Psoriasis is a kind of recurrent exerbation, with epidermal proliferation and inflammation for feature, FFI erythroderma desquamativum, its cause of disease with heredity, infect, allergy, dysbolismus and autoimmune etc. are relevant.This course of disease is long, and outward appearance is ugly, and the later stage can invade multiple internal organs, brings great damage to patient's body and mind.
Treat psoriatic medicine and comprise whole body system medication and local topical medicine.Early stage and that the state of an illness is lighter psoriasis mainly relies on external medication, and the psoriatic external used medicine for the treatment of mainly comprises at present:
1. vitamin D 3 analogs
Such medicine result in the change of psoriasis Topical therapy, and it can suppress various scytitis and epidermal proliferation, is conducive to the normal keratinization strengthening cell, clinical efficacy is better, but onset is slow, and average 6-8 Zhou Houcai has significant curative effect, main adverse reaction is that local skin stimulates.Such drug price is higher in addition, is a medical expense costly for the patient that skin lesion area is larger.
2. burnt oil-like formulations
Conventional has 2%-10% coal tar, pine tar, pityrol and Pityrol etc., has inhibitory action, therefore can treat psoriasis to the generation of smegma and epidermal basal cell mitosis and squama, but can carcinogenic and teratogenesis, is seldom applied to clinical at present.
3. anthraline preparation and corticosteroid formulations
Anthralin Ointment is coated with outward, and zest is stronger; Corticosteroid formulations can suppressor T cell activate, and reaches the psoriatic object for the treatment of, is the external curing medicine of main employing clinically at present.Although such medicine is rapid-action, side effect is comparatively large, and easily causes knock-on after drug withdrawal or be transformed into erythrodermic or psoriasis pustulosa.
Middle severe psoriasis needs Systemic administration, and such drug main will comprise anti-tumor agent, immunosuppressant, immunomodulator, tretinoin medicines, antibiotic and biological preparation etc.There is the safety of the large or prolonged application of side effect and the effectiveness still shortcoming such as indefinite more in these medicines.
Summary of the invention
The present invention is exactly that a kind of I (chlamydia) protein Pgp3 proposed suppresses the application in Pigs with Psoriasis medicine in preparation in order to solve existing medicine Problems existing in treatment psoriasis.
The present invention realizes according to following technical scheme.
I (chlamydia) protein Pgp3 suppresses the application in Pigs with Psoriasis medicine in preparation.
Described I (chlamydia) protein Pgp3 is combined with the mankind's antibacterial polypeptide LL-37 development suppressing psoriatic lesion.
Present invention obtains following beneficial effect.
The present invention effectively solves that the side effect of existing treatment psoriasis is large, long-term prescription patient Personal Safety and the problem such as drug effectiveness cannot ensure and medical expense is high.I (chlamydia) protein in the present invention derives from chlamydia trachomatis, and relative to chemicals, side effect is little, and therapeutic effect is obvious, is expected to substitute at present based on the curing psoriasis medicine of external hormone, has broad application prospects.
Accompanying drawing explanation
Fig. 1 is GST-Pgp3 protein SDS-PAGE electrophoresis detection figure of the present invention;
Fig. 2 is Pgp3 protein SDS-PAGE electrophoresis detection figure of the present invention;
Fig. 3 is SDS-PAGE electrophoresis detection figure after Pgp3 protein concentration of the present invention;
Fig. 4 is GST-pulldown experimental result picture of the present invention;
Fig. 5 is Pgp3 albumen patients before and after intervention mice Pigs with Psoriasis appearance comparison diagram of the present invention;
Fig. 6 is that Pgp3 albumen of the present invention intervention psoriasiform mouse experiment matched group skin lesion organizes HE colored graph;
Fig. 7 is that Pgp3 albumen of the present invention intervention psoriasiform mouse experiment model group skin lesion organizes HE colored graph;
Fig. 8 is that Pgp3 albumen of the present invention is intervened psoriasiform mouse experiment and is coated with high concentration group skin lesion outward and organizes HE colored graph;
Fig. 9 is that Pgp3 albumen of the present invention is intervened psoriasiform mouse experiment and is coated with low concentration group skin lesion outward and organizes HE colored graph;
Figure 10 is that Pgp3 albumen of the present invention is intervened psoriasiform mouse experiment and is coated with matched group skin lesion outward and organizes HE colored graph;
Figure 11 is that Pgp3 albumen of the present invention intervention psoriasiform mouse experiment injection high concentration group skin lesion organizes HE colored graph;
Figure 12 is that Pgp3 albumen of the present invention intervention psoriasiform mouse experiment injection low concentration group skin lesion organizes HE colored graph;
Figure 13 is that Pgp3 albumen of the present invention intervention psoriasiform mouse experiment injection matched group skin lesion organizes HE colored graph;
Figure 14 is Pgp3 albumen patients before and after intervention mice skin erythema integration trendgram of the present invention;
Figure 15 is Pgp3 albumen patients before and after intervention mice skin lesion area integral trendgram of the present invention;
Figure 16 is Pgp3 albumen patients before and after intervention mice skin lesion thickness integration trendgram of the present invention;
Figure 17 is Pgp3 albumen patients before and after intervention mice skin lesion total mark trendgram of the present invention.
Detailed description of the invention
One. nucleotide sequence and aminoacid sequence
1.Pgp3 albumen is encoded by chlamydia trachomatis plasmid pORF5, altogether 795bp (GeneID:3205528), and its nucleotide sequence is as follows:
ATGGGAAATTCTGGTTTTTATTTGTATAACACTGAAAACTGCGTCTTTGCTGATAATATCAAAGTTGGGCAAATGACAGAGCCGCTCAAGGACCAGCAAATAATCCTTGGGACAACATCAACACCTGTCGCAGCCAAAATGACAGCTTCTGATGGAATATCTTTAACAGTCTCCAATAATTCATCAACCAATGCTTCTATTACAATTGGTTTGGATGCGGAAAAAGCTTACCAGCTTATTCTAGAAAAGTTGGGAGATCAAATTCTTGATGGAATTGCTGATACTATTGTTGATAGTACAGTCCAAGATATTTTAGACAAAATCAAAACAGACCCTTCTCTAGGTTTGTTGAAAGCTTTTAACAACTTTCCAATCACTAATAAAATTCAATGCAACGGGTTATTCACTCCCAGTAACATTGAAACTTTATTAGGAGGAACTGAAATAGGAAAATTCACAGTCACACCCAAAAGCTCTGGGAGCATGTTCTTAGTCTCAGCAGATATTATTGCATCAAGAATGGAAGGCGGCGTTGTTCTAGCTTTGGTACGAGAAGGTGATTCTAAGCCCTGCGCGATTAGTTATGGATACTCATCAGGCATTCCTAATTTATGTAGTCTAAGAACCAGTATTACTAATACAGGATTGACTCCGACAACGTATTCATTACGTGTAGGCGGTTTAGAAAGCGGTGTGGTATGGGTTAATGCCCTTTCTAATGGCAATGATATTTTAGGAATAACAAATACTTCTAATGTATCTTTTTTAGAGGTAATACCTCAAACAAACGCTTAA
The molecular weight of 2.Pgp3 albumen is 29kDa, and its aminoacid sequence is as follows:
1mgnsgfylyntencvfadnikvgqmteplkdqqiilgttstpvaakmtasdgisltvsnn
61sstnasitigldaekayqlileklgdqildgiadtivdstvqdildkiktdpslgllkaf
121nnfpitnkiqcnglftpsnietllggteigkftvtpkssgsmflvsadiiasrmeggvvl
181alvregdskpcaisygyssgipnlcslrtsitntgltpttyslrvgglesgvvwvnalsn
241gndilgitntsnvsflevipqtna
The aminoacid sequence of 3.LL-37 albumen
1llgdffrkskekigkefkrivqrikdflrnlvprtes
4.PCR amplification Pgp3 genetic fragment primer
Primer
cGCGGATCCATGGGAAATTCTGGTTTTTATTTG
Primer
tTTTCCTTTGCGGCCGCTTAAGCGTTTGTTTGAGGTATTA
The preparation of two .Pgp3 albumen
The expression of 1.GST-Pgp3 albumen and qualification
1.1PCR amplification Pgp3 genetic fragment
With the strain of chlamydia trachomatis D type for template, with above-mentioned primer and primer
for primer, pcr amplification Pgp3 gene.PCR reaction condition: 92 DEG C of degeneration 30s; 55 DEG C of annealing 30s; 72 DEG C extend 30s, and last circulates 72 DEG C and extends 15min, total reaction volume 50ul, agarose gel electrophoresis qualification expression product.
The structure of 1.2 recombiant plasmid pGEX-6P-2-Pgp3
PCR primer and pGEX-6P-2 are carried out double digestion process with BamHI and NotI respectively, and T4 ligase connects 4h in 15 DEG C, builds pGEX-6P-2-Pgp3 recombiant plasmid, and is transformed into DH5 α bacterium (TIANGEN Biotech (Beijing) Co., Ltd.; CB101-02), with containing Amp
+selective agar medium filters out positive bacterium colony.By 1% sepharose electrophoresis and gene sequencing, the plasmid extracted in positive bacteria is identified.
The expression of 1.3 recombiant plasmid pGEX-6P-2-Pgp3
PGEX-6P-2-Pgp3 recombinant plasmid transformed is entered Escherichia coli BL21 (TIANGEN Biotech (Beijing) Co., Ltd.; CB105-01) in, add after SOC culture medium shakes up cultivation and proceed to LB solid medium, after 37 DEG C of overnight incubation, picking monoclonal bacterium colony adds the cultivation of LB liquid medium increment, to add after isopropyl-β-D-thiogalactoside (IPTG) abduction delivering 3h 4 DEG C, the centrifugal 5min of 12000rpm collects thalline, the resuspended precipitation of PBS buffer, add lysozyme, Triton-X100 mixes after cracking that ultrasonication thalline is transparent to suspension on ice, collected after centrifugation supernatant.
2.GST-Pgp3 purification
200ulGST magnetic bead (the GSTbeads through PBS buffer (pH7.4) prewashing is added in GST-Pgp3 albumen supernatant; GenScript bio tech ltd of the U.S.; L00327), 3000rpm, 4 DEG C of centrifugal 5min after shaken at room temperature lh also abandon supernatant, and with PBS buffer solution magnetic bead, supernatant carries out SDS-PAGE electrophoresis detection.As shown in Figure 1, the 3rd swimming lane is the GST-Pgp3 Protein Detection situation of the purification obtained after the absorption of GST magnetic bead, eluting to testing result, as seen at the object band that 54kDa place formation one is single.
In the absorption of GST magnetic bead, GST-Pgp3 protein solution after eluting, add 200ulPBS buffer and 10ulPP enzyme excise GST label, room temperature to be shaken after 2h centrifugal 5 minutes, collected by centrifugation Pgp3 supernatant, and carries out SDS-PAGE electrophoresis detection.As shown in Figure 2, GST-Pgp3 albumen is through PP proteolytic cleavage except after GST label, and SDS-PAGE electrophoresis showed is at 28kDa place appearance one article of protein band (the 3rd swimming lane).
Concentrating of 3.Pgp3 albumen
Pgp3 albumen after purification is added 10kDa super filter tube (Millipore Bioisystech Co., Ltd of the U.S.), add 10mlPBS buffer, 4 DEG C, 4000 × g is centrifugal, each 20min, repeats 5 times, collects the Pgp3 albumen after concentrating, SDS-PAGE electrophoresis detection.As shown in Figure 3, the Pgp3 albumen after 10kDa super filter tube concentrates, the protein band that SDS-PAGE electrophoresis detection is presented at the appearance of 28kDa place obviously increases slightly.
It is 5536ug/ml that BCA protein quantification test kit (Sai Mo flies generation that science and technology (China) company limited) measures protein concentration, and with PBS buffer, Pgp3 albumen is diluted to 100ug/ml and 50ug/ml respectively, subpackage ,-80 DEG C frozen for subsequent use.
Three .GSTpulldown experiments
1mlGST-Pgp3 albumen supernatant is mixed through the GST magnetic bead of PBS prewashing with 20ul, 3000rpm after shaken at room temperature lh, 4 DEG C of centrifugal 5min also abandon supernatant, supernatant is abandoned with after PBS buffer solution magnetic bead 3 times, 20ulGST-Pgp3 magnetic bead (GST-Pgp3beads) and 8ugLL-37 albumen (being synthesized by Peptide2.0 company) are hatched 30min jointly at 37 DEG C, centrifugal, with PBS buffer solution 3 times, each 10min, add SDS sample-loading buffer, boiling water bath boils 5min cooled on ice 5min, SDS-PAGE electrophoretic separation albumen, after electrophoresis, unload gel, soaked for transferring film buffer nitrocellulose filter is attached on the free surface of glue gently, 4 DEG C, 80V voltage transferring film 1 hour.After transferring film terminates, 1 × TBST washes film, and confining liquid closes 1 hour, adds anti-LL-37's
anti-4 DEG C of overnight incubation, add HRP labelling II anti-37 DEG C hatch 1h, darkroom exposure after luminous substrate effect 5min, to develop a film and record analysis.As shown in Figure 4, experimental result is as follows:
First swimming lane adds LL-37 albumen and reacts, and single protein band appears in 7kDa place, shows antibody specificity identification LL-37 albumen;
Second swimming lane adds GSTbeads and reacts, and does not occur protein band, shows antibody nonrecognition GST;
3rd swimming lane adds GSTbeads and LL-37 albumen and reacts, and does not occur protein band, show GST can not with LL-37 protein binding;
4th swimming lane adds GSTbeads and LL-37Sup. and reacts, 7kDa place occur single protein band, because of GST can not with LL-37 protein binding, LL-37 albumen is free in supernatant and is detected;
5th swimming lane adds GST-Pgp3beads and reacts, and does not occur protein band, shows antibody nonrecognition Pgp3 albumen;
6th swimming lane adds GST-Pgp3beads and LL-37 albumen and reacts, and in 7kDa place appearance one band, shows that Pgp3 albumen can in conjunction with LL-37 albumen; There is another band at 63kDa place, show GST-Pgp3 albumen can and LL-37 protein binding form stable compound;
7th swimming lane adds GST-Pgp3beads and LL-37Sup. and reacts, and faint band appears in 7kDa place, and because Pgp3 albumen can be combined with LL-37 and CRAMP, so supernatant dissociates, LL-37 amount is very low.
Four, the structure of psoriasiform mouse model and PASI scoring
4.1 laboratory animal preparations
Raising SPF level, body weight are the BALB/c female mice in 18-20g, 6-8 age in week.Strike off dorsal body setae and be about 2cm × 3cm size, single cage is raised, by group process after 1d.
4.2 experiment grouping and interventions
32 mices are divided into 8 groups at random, often organize 4, are respectively: blank group, model group, outer painting high concentration group, outer painting low concentration group, outer painting matched group, injection high concentration group, injection low concentration group, injection matched group.Detailed interference method is in table 1.
Note: 1.. mice 1d unhairing, starts with Pgp3 process, coprocessing 7 days on the 2nd day;
2. .IMQ modeling: morning every day is coated in mouse back by evenly outer for 42mg imiquimod at regular time and quantity;
3.. outer painting group: every day is coated with evenly outer for Pgp3 mixture at dusk at regular time and quantity;
4.. injection group: every day at dusk at regular time and quantity nine lattice methods by Pgp3 mixture multiple spot subcutaneous injection, every lattice 1 pin totally 9 pins.
As shown in Figure 5, the 8th day visible, and compared with blank group, model group mouse skin visible obviously erythema and squama, thickness significantly increases, and the similar Pigs with Psoriasis of perusal changes.Outer painting high and low concentration group, inject high and low concentration group mice skin lesion comparatively model group be improved in varying degrees, erythema shoals, squama reduces, skin is comparatively front smooth, epidermis thickens and alleviates, and is coated with and injects matched group outward and compare model group and have no notable difference, and erythema color is still darker, extensive squama, pachyderma still obviously.
4.3 laboratory animals are drawn materials
Each group of mice is drawn materials in process 8d through de-neck execution, and by nine lattice method clip corresponding region skin lesion tissues, prepare paraffin section after 10% formalin is fixing, HE dyes.
As shown in figs. 6-13, HE dyeing visible (HE × 200), compared with blank group, model group horny layer obviously thickens, be mainly hyperkeratosis, parakeratosis, spinous layer is thickening, and trochanterellus extends, the psoriasiform pathological changes such as lower end is broadening, partial fusion, skin corium inflammatory cell infiltration.After Pgp3 albumen is intervened, the high and low concentration group of outer painting, inject high and low concentration group mouse skin epidermal area smooth compared with model group, thickness comparatively intervenes front reduction, and parakeratosis alleviates.And the outer matched group and injection matched group and model group mice skin lesion histological appearance of being coated with is similar, epidermis is thicker, obvious parakeratosis and obviously inflammatory cell infiltration.
4.4 respectively group mice Pigs with Psoriasis area and disease severity (PASI) scorings
Timing every day observed and recorded skin lesion changes situation, and according to PASI standards of grading, give mice skin lesion place erythema, squama and infiltrate the different integrations such as thickened degree 0 ~ 4, standard is: 0: nothing; 1: slight; 2: moderate; 3: severe; 4: pole severe, three's summation draws total mark.Each group of mice integration average after drawing integration trendgram.
As shown in figures 14-17, PASI grade trend figure shows, and except blank group, after smearing imiquimod cream, each group mice score curve is obvious ascending tendency.Pgp3 albumen intervention groups PASI scoring is compared with model group, and curve presents and declines in various degree, and when the 8th day, every PASI Score index is all lower than model group.Outer painting and injection matched group curve are also positioned under model group, but decline degree is obviously not as Pgp3 intervention group.
4.5 statistical procedures
Experimental data with mean ± standard deviation (
± S) represent.Use SPSS19.0 software to data analysis, compare between many groups and adopt variance analysis (OneWayANOVA), inspection level α=0.05, P < 0.05 represents that difference has statistical significance.
Known to table 2, model group epidermal area obviously thickens, close to blank group epidermal thickness 10 times, outer painting and injection high concentration group epidermis thickened degree lower, compare with model group and have significant difference (P < 0.05), although outer painting and injection low concentration group skin thickness also comparatively model group obviously reduce, no difference of science of statistics (P > 0.05); And outer to be coated with and to inject matched group epidermis thickened degree still obvious.
In the present invention, why Pgp3 albumen has the psoriatic purposes for the treatment of, and reason is as follows:
Up-to-date research display mankind antimicrobial peptide LL-37 overexpression plays an important role in psoriatic generation with development, and the Histopathological characteristics that display is similar to psoriasis in the animal model of LL-37 overexpression.The relation of antimicrobial peptide LL-37 and onset of psoriasis is as follows:
1. be combined with self DNA, participate in plasmacytoid dendritic cells activation
Plasmacytoid dendritic cells (plasmacytoiddendriticcells, pDC) originates from lymphoid progenitors, is distributed in peripheral blood and lymphoid tissue, can high degree of specificity identification virus infect with certain micro-organisms.PDC does not distribute in normal circumference tissue, but obviously increases in the skin be inflamed, mucosa and tumor locus quantity.The specific expressed Toll-like receptor of pDCs (TLR) 7, TLR9, virus/microbial nucleic acids is identified within it in body, wherein TLR9 can non-methylated cytosine-phosphate-guanine motif in specific recognition CpGDN(DNA of bacteria), by MyD88-TRAF6-MAPK-NF-κ B signal transduction pathway, produce powerful type interferon (IFNs) reaction fast.The abnormal IFN produced is the main cause of pathologic autoimmune phenomena, mainly induction of the continuous maturation of periphery marrow dendritic cell, and then activation autoreactive T cell.
Under normal circumstances, pDCs does not react with self DNA.Virus waits the nucleic acid of microorganisms to contain to combine with it in a large number and activates the CpGDNA sequence of TLR9, but mammal self DNA major part is all methylated, few containing CpGDNA sequence.And recent self DNA of research display has the activity of potential activation TLR9, the reason why do not activated to be in self DNA endosome that can not enter containing TLR9, but related mechanism does not still understand.
There is pDCs in psoriatic's skin to infiltrate, the activation of pDCs is considered to " upstream " of inflammation or immunne response, then trigger autoimmune T cell activation, causes dermal inflammatory skin lesion to be formed.Can psoriasis be aggravated when skin sustains damage or stimulates, point out and discharge at skin lesion, self DNA and there is potential contact between the pDCs activation of local.
Up-to-date research display, Endogenous antimicrobial polypeptide LL-37 overexpression in psoriatic lesion is the key factor of pDCs activation in psoriatic lesion.This process relates to 3 independently steps.First, LL-37 makes it that configuration change occur by electrostatic interaction in conjunction with self DNA, forms the compact texture of polymerization; Secondly, LL-37 impels itself and self DNA complex to enter in the early endosome of pDC, has therefore walked around and has been positioned at the security mechanism that cell TLR9 identifies virus/microbial DNA and nonrecognition self DNA; Finally, the complex of itself and DNA is stayed in early endosome by LL-37, and may modify it in the process, thus the IFNs maintaining TLR9 mediation specifically produces.LL-37 has broken the congenital tolerance to self DNA, makes it by the approach similar to viral nucleic acid, and induction IFNs in rapid strong ground produces, and activates congenital and the acquired immune response further.Self DNA is discharged into outside born of the same parents in apoptosis process to have research to think, the common activating immune system of these DNA and LL-37, causes histologic lesion.Epithelial cell can activate by regulating the expression of LL-37 and maintain immunoreation in injured skin, strengthens its anti-infectious function and promotes wound healing to also have research to think.Thought that the infection rate at psoriatic lesion place was low in the past, be associated with the high expressed of LL-37.In fact, LL-37 is the main predisposing factors impelling IFNs to react in psoriatic lesion, and antibacterial defence system and psoriatic pathogenesis connect by first time.When skin sustains damage, epithelial cell LL-37 expression imbalance (overexpression) causes pDCs constantly to activate in psoriatic lesion, gathers, induction IFNs is abnormal to be produced, cause marrow maturing dendritic cell, inspire the pathologic autoimmunity reaction of local T cell mediation, cause psoriasis to occur.
2. promote epithelial hyperplasia and vascularization
It is a kind of epithelial cell growth factor that current LL-37 has been recognized.Tokumaru etc. report that LL-37 can induce epithelial cell growth factor receptor 2 body transcription activating, and impel KC to move.Promote that vascularization is another function of LL-37.Koczulla etc. are reported in the animal model of organize models and rabbit, and LL-37 can cause new vessels to be formed, and this vascularization mediated by endotheliocyte formylpeptidereceptor-like (FPRL)-1 receptor.KC hyperplasia, it is psoriatic Histopathological characteristics that dermal papilla telangiectasis, tortuous and new vessels are formed.Therefore LL-37 promotes that epithelial hyperplasia and angiopoietic effect may be relevant with the formation of psoriatic tissue Pathologic Characteristics.
3. the chemotaxis of pair inflammatory cell
The inflammatory cell infiltrations such as neutrophilic granulocyte, lymphocyte and histiocyte are another large Histopathological characteristics psoriatic.Chertov etc. report that LL37 centering granulocyte, mononuclear cell and T lymphocyte etc. have obvious chemotaxis.In addition, LL-37 can raise the expression of chemotactic cytokine IL-8 in macrophage, and can discharge LL-37 by the neutrophilic granulocyte that IL-8 stimulates, and the more inflammatory cell of further chemotactic is assembled.These effects of LL-37 are one of key factors causing inflammatory cell infiltration and the formation of neutrophilic granulocyte microabscess in psoriatic lesion.
Pgp3 albumen is the secreted protein of the about 28KDa encoded by chlamydia trachomatis, study through the present invention and find that Pgp3 albumen can in conjunction with LL-37, thus suppress the development of psoriatic lesion, and external and injection Pgp3 albumen all can reach identical effect.Therapeutic effect of the present invention is obvious, and toxic and side effects is little, is expected to substitute at present based on the curing psoriasis medicine of external hormone, has important scientific research and clinical value.
SEQUENCELISTING
The refined duckweed of <110> marquis
<120> I (chlamydia) protein Pgp3 suppresses the application in Pigs with Psoriasis medicine in preparation
<130>1
<160>1
<170>PatentInversion3.5
<210>1
<211>795
<212>DNA
<213>2AmbystomalateralexAmbystomajeffersonianum
<220>
<221> chlamydia trachomatis Pgp3
<222>(1)..(795)
<400>1
atgggaaattctggtttttatttgtataacactgaaaactgcgtctttgctgataatatc60
aaagttgggcaaatgacagagccgctcaaggaccagcaaataatccttgggacaacatca120
acacctgtcgcagccaaaatgacagcttctgatggaatatctttaacagtctccaataat180
tcatcaaccaatgcttctattacaattggtttggatgcggaaaaagcttaccagcttatt240
ctagaaaagttgggagatcaaattcttgatggaattgctgatactattgttgatagtaca300
gtccaagatattttagacaaaatcaaaacagacccttctctaggtttgttgaaagctttt360
aacaactttccaatcactaataaaattcaatgcaacgggttattcactcccagtaacatt420
gaaactttattaggaggaactgaaataggaaaattcacagtcacacccaaaagctctggg480
agcatgttcttagtctcagcagatattattgcatcaagaatggaaggcggcgttgttcta540
gctttggtacgagaaggtgattctaagccctgcgcgattagttatggatactcatcaggc600
attcctaatttatgtagtctaagaaccagtattactaatacaggattgactccgacaacg660
tattcattacgtgtaggcggtttagaaagcggtgtggtatgggttaatgccctttctaat720
ggcaatgatattttaggaataacaaatacttctaatgtatcttttttagaggtaatacct780
caaacaaacgcttaa795
<130>2
<160>1
<170>PatentInversion3.5
<210>1
<211>264
<212>PRT
<213>2AmbystomalateralexAmbystomajeffersonianum
<220>
<221> chlamydia trachomatis Pgp3 albumen
<222>(1)..(264)
<400>1
MetGlyAsnSerGlyPheTyrLeuTyrAsnThrGluAsnCysValPhe
151015
AlaAspAsnIleLysValGlyGlnMetThrGluProLeuLysAspGln
202530
GlnIleIleLeuGlyThrThrSerThrProValAlaAlaLysMetThr
354045
AlaSerAspGlyIleSerLeuThrValSerAsnAsnSerSerThrAsn
505560
AlaSerIleThrIleGlyLeuAspAlaGluLysAlaTyrGlnLeuIle
65707580
LeuGluLysLeuGlyAspGlnIleLeuAspGlyIleAlaAspThrIle
859095
ValAspSerThrValGlnAspIleLeuAspLysIleLysThrAspPro
100105110
SerLeuGlyLeuLeuLysAlaPheAsnAsnPheProIleThrAsnLys
115120125
IleGlnCysAsnGlyLeuPheThrProSerAsnIleGluThrLeuLeu
130135140
GlyGlyThrGluIleGlyLysPheThrValThrProLysSerSerGly
145150155160
SerMetPheLeuValSerAlaAspIleIleAlaSerArgMetGluGly
165170175
GlyValValLeuAlaLeuValArgGluGlyAspSerLysProCysAla
180185190
IleSerTyrGlyTyrSerSerGlyIleProAsnLeuCysSerLeuArg
195200205
ThrSerIleThrAsnThrGlyLeuThrProThrThrTyrSerLeuArg
210215220
ValGlyGlyLeuGluSerGlyValValTrpValAsnAlaLeuSerAsn
225230235240
GlyAsnAspIleLeuGlyIleThrAsnThrSerAsnValSerPheLeu
245250255
GluValIleProGlnThrAsnAla
260
<130>3
<160>1
<170>PatentInversion3.5
<210>1
<211>37
<212>PRT
<213>2AmbystomalateralexAmbystomajeffersonianum
<220>
<221>LL-37 albumen
<222>(1)..(37)
<400>1
LeuLeuGlyAspPhePheArgLysSerLysGluLysIleGlyLysGlu
151015
PheLysArgIleValGlnArgIleLysAspPheLeuArgAsnLeuVal
202530
ProArgThrGluSer
35
<130>4
<160>1
<170>PatentInversion3.5
<210>1
<211>33
<212>DNA
<213>2AmbystomalateralexAmbystomajeffersonianum
<220>
<221> primer I
<222>(1)..(33)
<400>1
cgcggatccatgggaaattctggtttttatttg33
<130>5
<160>1
<170>PatentInversion3.5
<210>1
<211>40
<212>DNA
<213>2AmbystomalateralexAmbystomajeffersonianum
<220>
<221> primer I I
<222>(1)..(40)
<400>1
ttttcctttgcggccgcttaagcgtttgtttgaggtatta40
SEQUENCELISTING
The refined duckweed of <110> marquis
<120> I (chlamydia) protein Pgp3 suppresses the application in Pigs with Psoriasis medicine in preparation
<130>1
<160>1
<170>PatentInversion3.5
<210>1
<211>795
<212>DNA
<213>2AmbystomalateralexAmbystomajeffersonianum
<220>
<221> chlamydia trachomatis Pgp3
<222>(1)..(795)
<400>1
atgggaaattctggtttttatttgtataacactgaaaactgcgtctttgctgataatatc60
aaagttgggcaaatgacagagccgctcaaggaccagcaaataatccttgggacaacatca120
acacctgtcgcagccaaaatgacagcttctgatggaatatctttaacagtctccaataat180
tcatcaaccaatgcttctattacaattggtttggatgcggaaaaagcttaccagcttatt240
ctagaaaagttgggagatcaaattcttgatggaattgctgatactattgttgatagtaca300
gtccaagatattttagacaaaatcaaaacagacccttctctaggtttgttgaaagctttt360
aacaactttccaatcactaataaaattcaatgcaacgggttattcactcccagtaacatt420
gaaactttattaggaggaactgaaataggaaaattcacagtcacacccaaaagctctggg480
agcatgttcttagtctcagcagatattattgcatcaagaatggaaggcggcgttgttcta540
gctttggtacgagaaggtgattctaagccctgcgcgattagttatggatactcatcaggc600
attcctaatttatgtagtctaagaaccagtattactaatacaggattgactccgacaacg660
tattcattacgtgtaggcggtttagaaagcggtgtggtatgggttaatgccctttctaat720
ggcaatgatattttaggaataacaaatacttctaatgtatcttttttagaggtaatacct780
caaacaaacgcttaa795
<130>2
<160>1
<170>PatentInversion3.5
<210>1
<211>264
<212>PRT
<213>2AmbystomalateralexAmbystomajeffersonianum
<220>
<221> chlamydia trachomatis Pgp3 albumen
<222>(1)..(264)
<400>1
MetGlyAsnSerGlyPheTyrLeuTyrAsnThrGluAsnCysValPhe
151015
AlaAspAsnIleLysValGlyGlnMetThrGluProLeuLysAspGln
202530
GlnIleIleLeuGlyThrThrSerThrProValAlaAlaLysMetThr
354045
AlaSerAspGlyIleSerLeuThrValSerAsnAsnSerSerThrAsn
505560
AlaSerIleThrIleGlyLeuAspAlaGluLysAlaTyrGlnLeuIle
65707580
LeuGluLysLeuGlyAspGlnIleLeuAspGlyIleAlaAspThrIle
859095
ValAspSerThrValGlnAspIleLeuAspLysIleLysThrAspPro
100105110
SerLeuGlyLeuLeuLysAlaPheAsnAsnPheProIleThrAsnLys
115120125
IleGlnCysAsnGlyLeuPheThrProSerAsnIleGluThrLeuLeu
130135140
GlyGlyThrGluIleGlyLysPheThrValThrProLysSerSerGly
145150155160
SerMetPheLeuValSerAlaAspIleIleAlaSerArgMetGluGly
165170175
GlyValValLeuAlaLeuValArgGluGlyAspSerLysProCysAla
180185190
IleSerTyrGlyTyrSerSerGlyIleProAsnLeuCysSerLeuArg
195200205
ThrSerIleThrAsnThrGlyLeuThrProThrThrTyrSerLeuArg
210215220
ValGlyGlyLeuGluSerGlyValValTrpValAsnAlaLeuSerAsn
225230235240
GlyAsnAspIleLeuGlyIleThrAsnThrSerAsnValSerPheLeu
245250255
GluValIleProGlnThrAsnAla
260
<130>3
<160>1
<170>PatentInversion3.5
<210>1
<211>37
<212>PRT
<213>2AmbystomalateralexAmbystomajeffersonianum
<220>
<221>LL-37 albumen
<222>(1)..(37)
<400>1
LeuLeuGlyAspPhePheArgLysSerLysGluLysIleGlyLysGlu
151015
PheLysArgIleValGlnArgIleLysAspPheLeuArgAsnLeuVal
202530
ProArgThrGluSer
35
<130>4
<160>1
<170>PatentInversion3.5
<210>1
<211>33
<212>DNA
<213>2AmbystomalateralexAmbystomajeffersonianum
<220>
<221> primer I
<222>(1)..(33)
<400>1
cgcggatccatgggaaattctggtttttatttg33
<130>5
<160>1
<170>PatentInversion3.5
<210>1
<211>40
<212>DNA
<213>2AmbystomalateralexAmbystomajeffersonianum
<220>
<221> primer I I
<222>(1)..(40)
<400>1
ttttcctttgcggccgcttaagcgtttgtttgaggtatta40
Claims (2)
1. the application of I (chlamydia) protein Pgp3 in preparation suppression Pigs with Psoriasis medicine.
2. I (chlamydia) protein Pgp3 according to claim 1 suppresses the application in Pigs with Psoriasis medicine in preparation, it is characterized in that: described I (chlamydia) protein Pgp3 is combined with the mankind's antibacterial polypeptide LL-37 development suppressing psoriatic lesion.
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|---|---|---|---|---|
| CN114177294A (en) * | 2021-12-14 | 2022-03-15 | 天津医科大学总医院 | Application of Chlamydia Protein Pgp3 in the Preparation of Drugs for Inhibiting Fallopian Tube Inflammation |
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| WO1995028487A2 (en) * | 1994-04-19 | 1995-10-26 | Biocine S.P.A. | Recombinant pgp3, methods of preparation and use in diagnosis and therapy |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114177294A (en) * | 2021-12-14 | 2022-03-15 | 天津医科大学总医院 | Application of Chlamydia Protein Pgp3 in the Preparation of Drugs for Inhibiting Fallopian Tube Inflammation |
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