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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 5/2009

Open Access 01-10-2009 | Research article

Suppressive effect of secretory phospholipase A2inhibitory peptide on interleukin-1β-induced matrix metalloproteinase production in rheumatoid synovial fibroblasts, and its antiarthritic activity in hTNFtg mice

Authors: Maung-Maung Thwin, Eleni Douni, Pachiappan Arjunan, George Kollias, Prem V Kumar, Ponnampalam Gopalakrishnakone

Published in: Arthritis Research & Therapy | Issue 5/2009

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Abstract

Introduction

Secretory phospholipase A2 (sPLA2) and matrix metalloproteinase (MMP) inhibitors are potent modulators of inflammation with therapeutic potential, but have limited efficacy in rheumatoid arthritis (RA). The objective of this study was to understand the inhibitory mechanism of phospholipase inhibitor from python (PIP)-18 peptide in cultured synovial fibroblasts (SF), and to evaluate its therapeutic potential in a human tumor necrosis factor (hTNF)-driven transgenic mouse (Tg197) model of arthritis.

Methods

Gene and protein expression of sPLA2-IIA, MMP-1, MMP-2, MMP-3, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 were analyzed by real time PCR and ELISA respectively, in interleukin (IL)-1β stimulated rheumatoid arthritis (RA) and osteoarthritis (OA) synovial fibroblasts cells treated with or without inhibitors of sPLA2 (PIP-18, LY315920) or MMPs (MMP Inhibitor II). Phosphorylation status of mitogen-activated protein kinase (MAPK) proteins was examined by cell-based ELISA. The effect of PIP-18 was compared with that of celecoxib, methotrexate, infliximab and antiflamin-2 in Tg197 mice after ip administration (thrice weekly for 5 weeks) at two doses (10, 30 mg/kg), and histologic analysis of ankle joints. Serum sPLA2 and cytokines (tumor necrosis factor (TNF)α, IL-6) were measured by Escherichia coli (E coli) assay and ELISA, respectively.

Results

PIP-18 inhibited sPLA2-IIA production and enzymatic activity, and suppressed production of MMPs in IL-1β-induced RA and OA SF cells. Treatment with PIP-18 blocked IL-1β-induced p38 MAPK phosphorylation and resulted in attenuation of sPLA2-IIA and MMP mRNA transcription in RA SF cells. The disease modifying effect of PIP-18 was evidenced by significant abrogation of synovitis, cartilage degradation and bone erosion in hTNF Tg197 mice.

Conclusions

Our results demonstrate the benefit that can be gained from using sPLA2 inhibitory peptide for RA treatment, and validate PIP-18 as a potential therapeutic in a clinically relevant animal model of human arthritis.
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Literature
1.
Bongartz TA, Sutton J, Sweeting MJ, Buchan I, Matteson EL, Montori V: Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. 2006, 295: 2275-2285. 10.1001/jama.295.19.2275.CrossRefPubMed
2.
Smolen JS, Aletaha D, Koeller M, Weisman MH, Emery P: New therapies for treatment of rheumatoid arthritis. Lancet. 2007, 370: 1861-1874. 10.1016/S0140-6736(07)60784-3.CrossRefPubMed
3.
Mohammed FF, Smookler DS, Khokha R: Metalloproteinases, inflammation, and rheumatoid arthritis. Ann Rheum Dis. 2003, 62 Suppl 2: ii43-ii47.PubMed
4.
Masuda S, Murakami M, Komiyama K, Ishihara M, Ishikawa Y, Ishii T, Kudo I: Various secretory phospholipase A2 enzymes are expressed in rheumatoid arthritis and augment prostaglandin production in cultured synovial cells. FEBS J. 2005, 272: 655-672. 10.1111/j.1742-4658.2004.04489.x.CrossRefPubMed
5.
Yedgar S, Cohen Y, Shoseyov D: Control of phospholipase A2 activities for the treatment of inflammatory conditions. Biochim Biophys Acta. 2006, 1761: 1373-1382.CrossRefPubMed
6.
Triggiani M, Granata F, Frattini A, Marone G: Activation of human inflammatory cells by secreted phospholipase A2 (A Review). Biochim Biophys Acta. 2006, 1761: 1289-1300.CrossRefPubMed
7.
Granata F, Balestrieri B, Petraroli A, Giannattasio G, Marone G, Triggiani M: Secretory phospholipases A2 as multivalent mediators of inflammatory and allergic disorders. Int Arch Allergy Immunol. 2003, 131: 153-163. 10.1159/000071481.CrossRefPubMed
8.
Thwin MM, Ong WY, Fong CW, Sato K, Kodama K, Farooqui AA, Gopalakrishnakone P: Secretory phospholipase A2 activity in the normal and kainate injected rat brain, and inhibition by a peptide derived from python serum. Exp Brain Res. 2003, 150: 427-433.PubMed
9.
Thwin MM, Gopalakrishnakone P, Kini RM, Armugam A, Jeyaseelan K: Recombinant antitoxic and antiinflammatory factor from the nonvenomous snake Python reticulatus: phospholipase A2 inhibition and venom neutralizing potential. Biochemistry. 2000, 39: 9604-9611. 10.1021/bi000395z.CrossRefPubMed
10.
Thwin MM, Douni E, Aidinis V, Kollias G, Kodama K, Sato K, Satish RL, Mahendran R, Gopalakrishnakone P: Effect of phospholipase A2 inhibitory peptide on inflammatory arthritis in a TNF transgenic mouse model: a time-course ultrastructural study. Arthritis Res Ther. 2004, 6: R282-294. 10.1186/ar1179.PubMedCentralCrossRefPubMed
11.
Thwin MM, Satyanarayanajois SD, Nagarajarao LM, Sato K, Arjunan P, Ramapatna SL, Kumar PV, Gopalakrishnakone P: Novel peptide inhibitors of human secretory phospholipase A2 with antiinflammatory activity: solution structure and molecular modeling. J Med Chem. 2007, 50: 5938-5950. 10.1021/jm070385x.CrossRefPubMed
12.
Burrage PS, Mix KS, Brinckerhoff CE: Matrix metalloproteinases: role in arthritis. Front Biosci. 2006, 11: 529-543. 10.2741/1817.CrossRefPubMed
13.
14.
Bradley JD, Dmitrienko AA, Kivitz AJ, Gluck OS, Weaver AL, Wiesenhutter C, Myers SL, Sides GD: A randomized, double-blinded, placebo-controlled clinical trial of LY333013 a selective inhibitor of group II secretory phospholipase A2, in the treatment of rheumatoid arthritis. J Rheumatol. 2005, 32: 417-423.PubMed
15.
Abraham E, Naum C, Bandi V, Gervich D, Lowry SF, Wunderink R, Schein RM, Macias W, Skerjanec S, Dmitrienko A, Farid N, Forgue ST, Jiang F: Efficacy and safety of LY315920Na/S- a selective inhibitor of 14-kDa group IIA secretory phospholipase A2, in patients with suspected sepsis and organ failure. Crit Care Med. 2003, 31: 718-728. 10.1097/01.CCM.0000053648.42884.89.CrossRefPubMed
16.
Keffer J, Probert L, Cazlaris H, Georgopoulos S, Kaslaris E, Kioussis D, Kollias G: Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. EMBO J. 1991, 10: 4025-4031.PubMedCentralPubMed
17.
Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988, 31: 315-324. 10.1002/art.1780310302.CrossRefPubMed
18.
Versteeg HH, Nijhuis E, Brink van den GR, Evertzen M, Pynaert GN, van Deventer SJ, Coffer PJ, Peppelenbosch MP: A new phosphospecific cell-based ELISA for p42/p44 mitogen-activated protein kinase (MAPK), p38 MAPK, protein kinase B and cAMP-response-element-binding protein. Biochem J. 2000, 350: 717-722. 10.1042/0264-6021:3500717.PubMedCentralCrossRefPubMed
19.
Pachiappan A, Thwin MM, Manikandan J, Gopalakrishnakone P: Glial inflammation and neurodegeneration induced by candoxin, a novel neurotoxin from Bungarus candidus venom: global gene expression analysis using microarray. Toxicon. 2005, 46: 883-899. 10.1016/j.toxicon.2005.08.017.CrossRefPubMed
20.
Livak KJ, Schmittge TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C (T)) method. Methods. 2001, 25: 402-408. 10.1006/meth.2001.1262.CrossRefPubMed
21.
Douni E, Sfikakis PP, Haralambous S, Fernandes P, Kollias G: Attenuation of inflammatory polyarthritis in TNF transgenic mice by diacerein: comparative analysis with dexamethasone, methotrexate and anti-TNF protocols. Arthritis Res Ther. 2004, 6: R65-R72. 10.1186/ar1028.PubMedCentralCrossRefPubMed
22.
Inglis JJ, Criado G, Medghalchi M, Andrews M, Sandison A, Feldmann M, Williams RO: Collagen-induced arthritis in C57BL/6 mice is associated with a robust and sustained T-cell response to type II collagen. Arthritis Res Ther. 2007, 9: R113-120. 10.1186/ar2319.PubMedCentralCrossRefPubMed
23.
Williams RO, Feldmann M, Maini RN: Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis. Proc Natl Acad Sci USA. 1992, 89: 9784-9788. 10.1073/pnas.89.20.9784.PubMedCentralCrossRefPubMed
24.
Gebhard HH, Zysk SP, Schmitt-Sody M, Jansson V, Messmer K, Veihelmann A: The effects of celecoxib on inflammation and synovial microcirculation in murine antigen-induced arthritis. Clin Exp Rheumatol. 2005, 23: 63-70.PubMed
25.
Snyder DW, Bach NJ, Dillard RD, Draheim SE, Carlson DG, Fox N, Roehm NW, Armstrong CT, Chang CH, Hartley LW, Johnson LM, Roman CR, Smith AC, Song M, Fleisch JH: Pharmacology of LY315920/S- [3-(aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl] oxy] acetate, a potent and selective secretory phospholipase A2 inhibitor: A new class of anti-inflammatory drugs, SPI. J Pharmacol Exp Ther. 1999, 288: 1117-1124.PubMed
26.
Pikul S, McDow Dunham KL, Almstead NG, De B, Natchus MG, Anastasio MV, McPhail SJ, Snider CE, Taiwo YO, Rydel T, Dunaway CM, Gu F, Mieling GE: Discovery of potent, achiral matrix metalloproteinase inhibitors. J Med Chem. 1998, 41: 3568-3571. 10.1021/jm980253r.CrossRefPubMed
27.
Peart MJ, Smyth GK, van Laar RK, Bowtell DD, Richon VM, Marks PA, Holloway AJ, Johnstone RW: Identification and functional significance of genes regulated by structurally different histone deacetylase inhibitors. Proc Natl Acad Sci USA. 2005, 102: 3697-3702. 10.1073/pnas.0500369102.PubMedCentralCrossRefPubMed
28.
Meyer MC, Rastogi P, Beckett CS, McHowat J: Phospholipase A2 inhibitors as potential anti-inflammatory agents. Curr Pharm Des. 2005, 11: 1301-1312. 10.2174/1381612053507521.CrossRefPubMed
29.
Fingleton B: Matrix metalloproteinases as valid clinical targets. Curr Pharm Des. 2007, 13: 333-346. 10.2174/138161207779313551.CrossRefPubMed
30.
Nuti E, Tuccinardi T, Rossello A: Matrix metalloproteinase inhibitors: new challenges in the era of post broad-spectrum inhibitors. Curr Pharm Des. 2007, 13: 2087-2100. 10.2174/138161207781039706.CrossRefPubMed
31.
Murphy G, Nagase H: Reappraising metalloproteinases in rheumatoid arthritis and osteoarthritis:destruction or repair?. Nat Clin Pract Rheumatol. 2008, 4: 128-135. 10.1038/ncprheum0727.CrossRefPubMed
32.
Pruzanski W: Phospholipase A2: quo vadis?. J Rheumatol. 2005, 32: 400-402.PubMed
33.
Schevitz RW, Bach NJ, Carlson DG, Chirgadze NY, Clawson DK, Dillard RD, Draheim SE, Hartley LW, Jones ND, Mihelich ED, Olkowski JL, Snyder DW, Sommers C, Wery JP: Structure-based design of the first potent and selective inhibitor of human non-pancreatic secretory phospholipase A2. Nat Struct Biol. 1995, 2: 458-465. 10.1038/nsb0695-458.CrossRefPubMed
34.
Hulkower KI, Wertheimer SJ, Levin W, Coffey JW, Anderson CM, Chen T, DeWitt DL, Crowl RM, Hope WC, Morgan DW: Interleukin-1 beta induces cytosolic phospholipase A2 and prostaglandin H synthase in rheumatoid synovial fibroblasts. Evidence for their roles in the production of prostaglandin E2. Arthritis Rheum. 1994, 37: 653-661. 10.1002/art.1780370508.CrossRefPubMed
35.
Bidgood MJ, Jamal OS, Cunningham AM, Brooks PM, Scott KF: Type IIA secretory phospholipase A2 up-regulates cyclooxygenase-2 and amplifies cytokine-mediated prostaglandin production in human rheumatoid synoviocytes. J Immunol. 2000, 165: 2790-2797.CrossRefPubMed
36.
Lee C, Lee J, Choi YA, Kang SS, Baek SH: cAMP elevating agents suppress secretory phospholipase A(2)-induced matrix metalloproteinase-2 activation. Biochem Biophys Res Commun. 2006, 340: 1278-1283. 10.1016/j.bbrc.2005.12.136.CrossRefPubMed
37.
Thalhamer T, McGrath MA, Harnett MM: MAPKs and their relevance to arthritis and inflammation. Rheumatology (Oxford). 2008, 47: 409-414. 10.1093/rheumatology/kem297.CrossRef
38.
Ravanti L, Heino J, López-Otín C, Kähäri VM: Induction of collagenase-3 (MMP-13) expression in human skin fibroblasts by three-dimensional collagen is mediated by p38 mitogen-activated protein kinase. J Biol Chem. 1999, 274: 2446-2455. 10.1074/jbc.274.4.2446.CrossRefPubMed
39.
Reunanen N, Li SP, Ahonen M, Foschi M, Han J, Kähäri VM: Activation of p38 alpha MAPK enhances collagenase-1 (matrix metalloproteinase (MMP)-1) and stromelysin-1 (MMP-3) expression by mRNA stabilization. J Biol Chem. 2002, 277: 32360-32368. 10.1074/jbc.M204296200.CrossRefPubMed
40.
Xie Z, Singh M, Singh K: Differential regulation of matrix metalloproteinase-2 and -9 expression and activity in adult rat cardiac fibroblasts in response to interleukin-1beta. J Biol Chem. 2004, 279: 39513-39519. 10.1074/jbc.M405844200.CrossRefPubMed
41.
Brown RD, Jones GM, Laird RE, Hudson P, Long CS: Cytokines regulate matrix metalloproteinases and migration in cardiac fibroblasts. Biochem Biophys Res Commun. 2007, 362: 200-205. 10.1016/j.bbrc.2007.08.003.PubMedCentralCrossRefPubMed
42.
Westra J, Limburg PC, de Boer P, van Rijswijk MH: Effects of RWJ 6 a p38 mitogen activated protein kinase (MAPK) inhibitor, on the production of inflammatory mediators by rheumatoid synovial fibroblasts. Ann Rheum Dis. 2004, 63: 1453-1459. 10.1136/ard.2003.013011.PubMedCentralCrossRefPubMed
43.
Müller-Ladner U, Ospelt C, Gay S, Distler O, Pap T: Cells of the synovium in rheumatoid arthritis. Synovial fibroblasts. Arthritis Res Ther. 2007, 9: 223-212. 10.1186/ar2337.PubMedCentralCrossRefPubMed
44.
Corcoran ML, Hewitt RE, Kleiner DE, Stetler-Stevenson WG: MMP-2: expression, activation and inhibition. Enzyme Protein. 1996, 49: 7-19.PubMed
45.
Church WB, Inglis AS, Tseng A, Duell R, Lei PW, Bryant KJ, Scott KF: A novel approach to the design of inhibitors of human secreted phospholipase A2 based on native peptide inhibition. J Biol Chem. 2001, 276: 33156-33164. 10.1074/jbc.M101272200.CrossRefPubMed
46.
Vincenti MP, Brinckerhoff CE: Transcriptional regulation of collagenase (MMP-1, MMP-13) genes in arthritis: integration of complex signaling pathways for the recruitment of gene-specific transcription factors. Arthritis Res. 2002, 4: 157-164. 10.1186/ar401.PubMedCentralCrossRefPubMed
47.
Kuwata H, Nonaka T, Murakami M, Kudo I: Search of factors that intermediate cytokine-induced group IIA phospholipase A2 expression through the cytosolic phospholipase A2- and 12/15-lipoxygenase-dependent pathway. J Biol Chem. 2005, 280: 25830-25839. 10.1074/jbc.M500168200.CrossRefPubMed
48.
Zenz R, Eferl R, Scheinecker C, Redlich K, Smolen J, Schonthaler HB, Kenner L, Tschachler E, Wagner EF: Activator protein 1 (Fos/Jun) functions in inflammatory bone and skin disease. Arthritis Res Ther. 2008, 10: 201-210. 10.1186/ar2338.PubMedCentralCrossRefPubMed
49.
Korb A, Tohidast-Akrad M, Cetin E, Axmann R, Smolen J, Schett G: Differential tissue expression and activation of p38 MAPK alpha, beta, gamma, and delta isoforms in rheumatoid arthritis. Arthritis Rheum. 2006, 54: 2745-2756. 10.1002/art.22080.CrossRefPubMed
50.
Schett G, Zwerina J, Firestein G: The p38 mitogen-activated protein kinase (MAPK) pathway in rheumatoid arthritis. Ann Rheum Dis. 2008, 67: 909-916. 10.1136/ard.2007.074278.PubMedCentralCrossRefPubMed
51.
Mounier CM, Ghomashchi F, Lindsay MR, James S, Singer AG, Parton RG, Gelb MH: Arachidonic acid release from mammalian cells transfected with human groups IIA and X secreted phospholipase A(2) occurs predominantly during the secretory process and with the involvement of cytosolic phospholipase A(2)-alpha. J Biol Chem. 2004, 279: 25024-25038. 10.1074/jbc.M313019200.CrossRefPubMed
52.
Han WK, Sapirstein A, Hung CC, Alessandrini A, Bonventre JV: Cross-talk between cytosolic phospholipase A2 alpha (cPLA2 alpha) and secretory phospholipase A2 (sPLA2) in hydrogen peroxide-induced arachidonic acid release in murine mesangial cells: sPLA2 regulates cPLA2 alpha activity that is responsible for arachidonic acid release. J Biol Chem. 2003, 278: 24153-24163. 10.1074/jbc.M300424200.CrossRefPubMed
53.
Huwiler A, Staudt G, Kramer RM, Pfeilschifter J: Cross-talk between secretory phospholipase A2 and cytosolic phospholipase A2 in rat renal mesangial cells. Biochim Biophys Acta. 1997, 1348: 257-272.CrossRefPubMed
54.
U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER): Guidance for Industry Clinical Development Programs for Drugs, Devices, and Biological Products for the Treatment of Rheumatoid Arthritis (RA). 1999, FDA, Silver Spring, MD, USA
55.
Wada Y, Nakajima-Yamada T, Yamada K, Tsuchida J, Yasumoto T, Shimozato T, Aoki K, Kimura T, Ushiyama S: R-13 a novel inhibitor of p38 MAPK, ameliorates hyperalgesia and swelling in arthritis models. Eur J Pharmacol. 2005, 506: 285-295. 10.1016/j.ejphar.2004.11.013.CrossRefPubMed
56.
Patten C, Bush K, Rioja I, Morgan R, Wooley P, Trill J, Life P: Characterization of pristane-induced arthritis, a murine model of chronic disease: response to antirheumatic agents, expression of joint cytokines, and immunopathology. Arthritis Rheum. 2004, 50: 3334-3345. 10.1002/art.20507.CrossRefPubMed
57.
Butler DM, Malfait AM, Mason LJ, Warden PJ, Kollias G, Maini RN, Feldmann M, Brennan FM: DBA/1 mice expressing the human TNF-alpha transgene develop a severe, erosive arthritis: characterization of the cytokine cascade and cellular composition. J Immunol. 1997, 159: 2867-2876.PubMed
58.
Penglis PS, Cleland LG, Demasi M, Caughey GE, James MJ: Differential regulation of prostaglandin E2 and thromboxane A2 production in human monocytes: implications for the use of cyclooxygenase inhibitors. J Immunol. 2000, 165: 1605-1611.CrossRefPubMed
59.
Moreno JJ: Antiflammin peptides in the regulation of inflammatory response. Ann N Y Acad Sci. 2000, 923: 147-153.CrossRefPubMed
60.
Saito H, Kojima T, Takahashi M, Horne WC, Baron R, Amagasa T, Ohya K, Aoki K: A tumor necrosis factor receptor loop peptide mimic inhibits bone destruction to the same extent as anti-tumor necrosis factor monoclonal antibody in murine collagen-induced arthritis. Arthritis Rheum. 2007, 56: 1164-1174. 10.1002/art.22495.CrossRefPubMed
61.
Beck S, Lambeau G, Scholz-Pedretti K, Gelb MH, Janssen MJ, Edwards SH, Wilton DC, Pfeilschifter J, Kaszkin M: Potentiation of tumor necrosis factor alpha-induced secreted phospholipase A2(sPLA2)-IIA expression in mesangial cells by an autocrine loop involving sPLA2 and peroxisome proliferator-activated receptor alpha activation. J Biol Chem. 2003, 278: 29799-29812. 10.1074/jbc.M211763200.CrossRefPubMed
62.
Pruzanski W, Bogoch E, Katz A, Wloch M, Stefanski E, Grouix B, Sakotic G, Vadas P: Induction of release of secretory nonpancreatic phospholipase A2 from human articular chondrocytes. J Rheumatol. 1995, 22: 2114-2119.PubMed
63.
Leistad L, Feuerherm AJ, Ostensen M, Faxvaag A, Johansen B: Presence of secretory group IIa and V phospholipase A2 and cytosolic group IV alpha phospholipase A2 in chondrocytes from patients with rheumatoid arthritis. Clin Chem Lab Med. 2004, 42: 602-610. 10.1515/CCLM.2004.104.CrossRefPubMed
64.
Cho TJ, Lehmann W, Edgar C, Sadeghi C, Hou A, Einhorn TA, Gerstenfeld LC: Tumor necrosis factor alpha activation of the apoptotic cascade in murine articular chondrocytes is associated with the induction of metalloproteinases and specific pro-resorptive factors. Arthritis Rheum. 2003, 48: 2845-2854. 10.1002/art.11390.CrossRefPubMed
65.
Zwerina J, Tuerk B, Redlich K, Smolen JS, Schett G: Imbalance of local bone metabolism in inflammatory arthritis and its reversal upon tumor necrosis factor blockade: direct analysis of bone turnover in murine arthritis. Arthritis Res Ther. 2006, 8: R22-32. 10.1186/ar1872.PubMedCentralCrossRefPubMed
66.
Tian L, Stefanidakis M, Ning L, Van Lint P, Nyman-Huttunen H, Libert C, Itohara S, Mishina M, Rauvala H, Gahmberg CG: Activation of NMDA receptors promotes dendritic spine development through MMP-mediated ICAM-5 cleavage. J Cell Biol. 2007, 178: 687-700. 10.1083/jcb.200612097.PubMedCentralCrossRefPubMed
67.
Wang XB, Bozdagi O, Nikitczuk JS, Zhai ZW, Zhou Q, Huntley GW: Extracellular proteolysis by matrix metalloproteinase-9 drives dendritic spine enlargement and long-term potentiation coordinately. Proc Natl Acad Sci USA. 2008, 105: 19520-19525. 10.1073/pnas.0807248105.PubMedCentralCrossRefPubMed
Metadata
Title
Suppressive effect of secretory phospholipase A2inhibitory peptide on interleukin-1β-induced matrix metalloproteinase production in rheumatoid synovial fibroblasts, and its antiarthritic activity in hTNFtg mice
Authors
Maung-Maung Thwin
Eleni Douni
Pachiappan Arjunan
George Kollias
Prem V Kumar
Ponnampalam Gopalakrishnakone
Publication date
01-10-2009
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 5/2009
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar2810

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