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The TNF superfamily member LIGHT contributes to survival and activation of synovial fibroblasts in rheumatoid arthritis.
Rheumatology (Oxford). 2007 Jul; 46(7):1063-70.R

Abstract

OBJECTIVES

The TNF superfamily member LIGHT has a T-cell co-stimulatory role and has previously been associated with inflammation and autoimmunity. To investigate its role in rheumatoid arthritis (RA), a disease where activated T cells contribute in a prominent way, we have analysed the expression of LIGHT and its receptors in RA and analysed its effects on synovial fibroblasts in vitro.

METHODS

The expression of LIGHT was measured in synovial tissues and fluids and the receptors of LIGHT were detected on synovial fibroblasts derived from patients with RA and osteoarthritis (OA). The effects of recombinant LIGHT on the production of proinflammatory cytokines and proteases and on the apoptosis of synovial fibroblasts was assessed.

RESULTS

LIGHT mRNA was present in synovial tissues of patients with RA but not with OA. Correspondingly, soluble LIGHT protein could be detected in RA synovial fluid samples at much higher levels than in synovial fluid from patients with OA. Immunohistochemical detection of LIGHT and analysis of synovial fluid cells by flow cytometry revealed CD4 T cells as the major source of LIGHT in the rheumatoid joint. Synovial fibroblasts from RA patients were found to express the LIGHT receptors HVEM and LTbetaR. Recombinant LIGHT induced RA synovial fibroblasts to upregulate MMP-9 mRNA, CD54 and IL-6 in an NF-kappaB-dependent fashion. In vitro, exposure of cultured synovial fibroblasts to LIGHT reduced FAS-mediated apoptosis significantly, without affecting the rate of spontaneous apoptosis.

CONCLUSIONS

The results provide evidence for a novel T-cell-dependent activation of synovial fibroblasts by LIGHT in joints of patients with RA, contributing to an inflammatory and destructive phenotype.

Authors+Show Affiliations

Center of Experimental Rheumatology, Department of Rheumatology, University Hospital of Zurich, Gloriastrasse 25, 8091 Zurich, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17426140

Citation

Pierer, M, et al. "The TNF Superfamily Member LIGHT Contributes to Survival and Activation of Synovial Fibroblasts in Rheumatoid Arthritis." Rheumatology (Oxford, England), vol. 46, no. 7, 2007, pp. 1063-70.
Pierer M, Brentano F, Rethage J, et al. The TNF superfamily member LIGHT contributes to survival and activation of synovial fibroblasts in rheumatoid arthritis. Rheumatology (Oxford). 2007;46(7):1063-70.
Pierer, M., Brentano, F., Rethage, J., Wagner, U., Hantzschel, H., Gay, R. E., Gay, S., & Kyburz, D. (2007). The TNF superfamily member LIGHT contributes to survival and activation of synovial fibroblasts in rheumatoid arthritis. Rheumatology (Oxford, England), 46(7), 1063-70.
Pierer M, et al. The TNF Superfamily Member LIGHT Contributes to Survival and Activation of Synovial Fibroblasts in Rheumatoid Arthritis. Rheumatology (Oxford). 2007;46(7):1063-70. PubMed PMID: 17426140.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The TNF superfamily member LIGHT contributes to survival and activation of synovial fibroblasts in rheumatoid arthritis. AU - Pierer,M, AU - Brentano,F, AU - Rethage,J, AU - Wagner,U, AU - Hantzschel,H, AU - Gay,R E, AU - Gay,S, AU - Kyburz,D, Y1 - 2007/04/10/ PY - 2007/4/12/pubmed PY - 2007/9/18/medline PY - 2007/4/12/entrez SP - 1063 EP - 70 JF - Rheumatology (Oxford, England) JO - Rheumatology (Oxford) VL - 46 IS - 7 N2 - OBJECTIVES: The TNF superfamily member LIGHT has a T-cell co-stimulatory role and has previously been associated with inflammation and autoimmunity. To investigate its role in rheumatoid arthritis (RA), a disease where activated T cells contribute in a prominent way, we have analysed the expression of LIGHT and its receptors in RA and analysed its effects on synovial fibroblasts in vitro. METHODS: The expression of LIGHT was measured in synovial tissues and fluids and the receptors of LIGHT were detected on synovial fibroblasts derived from patients with RA and osteoarthritis (OA). The effects of recombinant LIGHT on the production of proinflammatory cytokines and proteases and on the apoptosis of synovial fibroblasts was assessed. RESULTS: LIGHT mRNA was present in synovial tissues of patients with RA but not with OA. Correspondingly, soluble LIGHT protein could be detected in RA synovial fluid samples at much higher levels than in synovial fluid from patients with OA. Immunohistochemical detection of LIGHT and analysis of synovial fluid cells by flow cytometry revealed CD4 T cells as the major source of LIGHT in the rheumatoid joint. Synovial fibroblasts from RA patients were found to express the LIGHT receptors HVEM and LTbetaR. Recombinant LIGHT induced RA synovial fibroblasts to upregulate MMP-9 mRNA, CD54 and IL-6 in an NF-kappaB-dependent fashion. In vitro, exposure of cultured synovial fibroblasts to LIGHT reduced FAS-mediated apoptosis significantly, without affecting the rate of spontaneous apoptosis. CONCLUSIONS: The results provide evidence for a novel T-cell-dependent activation of synovial fibroblasts by LIGHT in joints of patients with RA, contributing to an inflammatory and destructive phenotype. SN - 1462-0324 UR - https://www.unboundmedicine.com/medline/citation/17426140/The_TNF_superfamily_member_LIGHT_contributes_to_survival_and_activation_of_synovial_fibroblasts_in_rheumatoid_arthritis_ L2 - https://academic.oup.com/rheumatology/article-lookup/doi/10.1093/rheumatology/kem063 DB - PRIME DP - Unbound Medicine ER -