Induction of metalloproteinases expression by TLR ligands in human fibroblast like synoviocytes from juvenile idiopathic arthritis patients.

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dc.contributor.authorAgarwal, Shilpi
dc.contributor.authorMisra, Ramnath
dc.contributor.authorAggarwal, Amita
dc.date.accessioned2011-11-29T06:44:08Z
dc.date.available2011-11-29T06:44:08Z
dc.date.issued2010-06
dc.description.abstractBackground & objective: Juvenile idiopathic arthritis (JIA) is characterized by chronic synovitis, cartilage damage and bone erosion. Both genetic and environmental factors and microbes probably play a role in pathogenesis. Microbes are recognized by Toll like receptors (TLRs) and activate innate immune response. We studied the ability of bacterial and viral products to produce matrix metalloproteinases (MMPs) and cytokines by fibroblast like synoviocytes (FLS) from patients with JIA. Methods: FLS were cultured from synovial fluid (SF) of patients with JIA and subsequently stimulated for 48 h by different TLR ligands [peptidoglycan (PG) for TLR2, poly(I-C) for TLR3, lipopolysaccharide (LPS) for TLR4, flagellin for TLR5, imiquimod for TLR7 and CpG DNA for TLR9]. Later the production of IL6, IL8, MMP-1, MMP-3, tissue inhibitors of metalloproteinase (TIMP1) was measured in the culture supernatants by ELISA. Expression of TLR2, TLR4, TLR7 and TLR9 was studied in FLS derived from JIA patients by RT-PCR. Results: IL6, IL8, MMP3 and MMP1 production was induced on stimulation of FLS with TLR2 ligand, TLR3 ligand, TLR4 ligand, TLR5 ligand but not with TLR7 ligand and TLR9 ligand. There was no effect of these ligands on the production of TIMP thus the balance was tilted in favour of MMPs after TLR ligation. TLR2, TLR4 and low expression of TLR9 was found but, no expression of TLR7 was found in FLS from JIA patients. Interpretation & conclusion: TLR pathway stimulation by microbial products or endogenous ligands could be involved in the production of MMPs in JIA and may contribute to disease pathology. Thus it may be beneficial to inhibit TLR pathway to reduce cartilage destruction.en_US
dc.identifier.citationAgarwal Shilpi, Misra Ramnath, Aggarwal Amita. Induction of metalloproteinases expression by TLR ligands in human fibroblast like synoviocytes from juvenile idiopathic arthritis patients. Indian Journal of Medical Research. 2010 Jun; 131(6): 771-779.en_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/135517
dc.language.isoenen_US
dc.source.urihttps://icmr.nic.in/ijmr/2010/june/0606.pdfen_US
dc.subjectArthritisen_US
dc.subjectcollagenasesen_US
dc.subjectinflammationen_US
dc.subjectinnate immunityen_US
dc.subjectmetalloproteinaseen_US
dc.subjectsynovitisen_US
dc.subjectToll like receptoren_US
dc.subject.meshAnimals
dc.subject.meshArthritis, Juvenile Rheumatoid --enzymology
dc.subject.meshArthritis, Juvenile Rheumatoid --immunology
dc.subject.meshArthritis, Juvenile Rheumatoid --pathology
dc.subject.meshCells, Cultured
dc.subject.meshCytokines --genetics
dc.subject.meshCytokines --metabolism
dc.subject.meshFibroblasts --cytology
dc.subject.meshFibroblasts --physiology
dc.subject.meshHumans
dc.subject.meshImmunity, Innate --immunology
dc.subject.meshLigands
dc.subject.meshMatrix Metalloproteinases --genetics
dc.subject.meshMatrix Metalloproteinases --metabolism
dc.subject.meshSynovial Fluid --cytology
dc.subject.meshToll-Like Receptors --genetics
dc.subject.meshToll-Like Receptors --metabolism
dc.titleInduction of metalloproteinases expression by TLR ligands in human fibroblast like synoviocytes from juvenile idiopathic arthritis patients.en_US
dc.typeArticleen_US
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