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Effects of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) on the expression of inflammatory cytokines and apoptosis induction in rheumatoid synovial fibroblasts and monocytes.
J Autoimmun. 2001 Nov; 17(3):215-21.JA

Abstract

This study was performed to investigate whether peroxisome proliterator-activated receptor-gamma (PPAR-gamma) exerted an anti-inflammatory effect on rheumatoid synovial cells and inhibited dysregulated proliferation. The expression of PPAR-gamma mRNA in cultured human synoviocytes and THP-1 cells was analysed by RT-PCR. PPAR-gamma was expressed in normal, osteoarthritis (OA), rheumatoid arthritis (RA) synovial cells as well as a human monocytic cell line, THP-1. In RA and OA synoviocytes, the induction of inflammatory cytokine mRNA expression such as TNF-alpha and IL-1beta was significantly inhibited by the natural PPAR-gamma agonist, 15 deoxy-Delta(12,14)prostaglandin J(2)(15d-PGJ(2)). The effect of PPAR-gamma on the nuclear factor (NF)-kappaB activity was tested by electrophoretic mobility shift assay (EMSA). Both troglitazone and 15d-PGJ(2)markedly inhibited TNF-alpha-induced NF-kappaB activation at 30 microM. However, PPAR-gamma agonist neither reduced proliferation nor induced apoptosis in RA synoviocytes when measured by XTT assay and fluorescence activated cell sorter (FACS) analysis. In contrast, it induced apoptosis in a dose-dependent manner in THP-1 cells and augmented TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis as well. In conclusion, these data demonstrate that PPAR-gamma is expressed in human synoviocytes and THP-1 cells, and the PPAR-gamma activation inhibits expression of inflammatory cytokines in RA synoviocytes. Furthermore, PPAR-gamma activation induces apoptosis by itself and augments TRAIL/Apo2L-induced apoptosis in THP-1 cells. These results suggest that PPAR-gamma agonists may provide a new therapeutic approach for RA.

Authors+Show Affiliations

Department of Biochemistry, Korea University College of Medicine, Sungbuk-Gu, Seoul, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11712859

Citation

Ji, J D., et al. "Effects of Peroxisome Proliferator-activated Receptor-gamma (PPAR-gamma) On the Expression of Inflammatory Cytokines and Apoptosis Induction in Rheumatoid Synovial Fibroblasts and Monocytes." Journal of Autoimmunity, vol. 17, no. 3, 2001, pp. 215-21.
Ji JD, Cheon H, Jun JB, et al. Effects of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) on the expression of inflammatory cytokines and apoptosis induction in rheumatoid synovial fibroblasts and monocytes. J Autoimmun. 2001;17(3):215-21.
Ji, J. D., Cheon, H., Jun, J. B., Choi, S. J., Kim, Y. R., Lee, Y. H., Kim, T. H., Chae, I. J., Song, G. G., Yoo, D. H., Kim, S. Y., & Sohn, J. (2001). Effects of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) on the expression of inflammatory cytokines and apoptosis induction in rheumatoid synovial fibroblasts and monocytes. Journal of Autoimmunity, 17(3), 215-21.
Ji JD, et al. Effects of Peroxisome Proliferator-activated Receptor-gamma (PPAR-gamma) On the Expression of Inflammatory Cytokines and Apoptosis Induction in Rheumatoid Synovial Fibroblasts and Monocytes. J Autoimmun. 2001;17(3):215-21. PubMed PMID: 11712859.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) on the expression of inflammatory cytokines and apoptosis induction in rheumatoid synovial fibroblasts and monocytes. AU - Ji,J D, AU - Cheon,H, AU - Jun,J B, AU - Choi,S J, AU - Kim,Y R, AU - Lee,Y H, AU - Kim,T H, AU - Chae,I J, AU - Song,G G, AU - Yoo,D H, AU - Kim,S Y, AU - Sohn,J, PY - 2001/11/20/pubmed PY - 2002/1/18/medline PY - 2001/11/20/entrez SP - 215 EP - 21 JF - Journal of autoimmunity JO - J Autoimmun VL - 17 IS - 3 N2 - This study was performed to investigate whether peroxisome proliterator-activated receptor-gamma (PPAR-gamma) exerted an anti-inflammatory effect on rheumatoid synovial cells and inhibited dysregulated proliferation. The expression of PPAR-gamma mRNA in cultured human synoviocytes and THP-1 cells was analysed by RT-PCR. PPAR-gamma was expressed in normal, osteoarthritis (OA), rheumatoid arthritis (RA) synovial cells as well as a human monocytic cell line, THP-1. In RA and OA synoviocytes, the induction of inflammatory cytokine mRNA expression such as TNF-alpha and IL-1beta was significantly inhibited by the natural PPAR-gamma agonist, 15 deoxy-Delta(12,14)prostaglandin J(2)(15d-PGJ(2)). The effect of PPAR-gamma on the nuclear factor (NF)-kappaB activity was tested by electrophoretic mobility shift assay (EMSA). Both troglitazone and 15d-PGJ(2)markedly inhibited TNF-alpha-induced NF-kappaB activation at 30 microM. However, PPAR-gamma agonist neither reduced proliferation nor induced apoptosis in RA synoviocytes when measured by XTT assay and fluorescence activated cell sorter (FACS) analysis. In contrast, it induced apoptosis in a dose-dependent manner in THP-1 cells and augmented TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis as well. In conclusion, these data demonstrate that PPAR-gamma is expressed in human synoviocytes and THP-1 cells, and the PPAR-gamma activation inhibits expression of inflammatory cytokines in RA synoviocytes. Furthermore, PPAR-gamma activation induces apoptosis by itself and augments TRAIL/Apo2L-induced apoptosis in THP-1 cells. These results suggest that PPAR-gamma agonists may provide a new therapeutic approach for RA. SN - 0896-8411 UR - https://www.unboundmedicine.com/medline/citation/11712859/Effects_of_peroxisome_proliferator_activated_receptor_gamma__PPAR_gamma__on_the_expression_of_inflammatory_cytokines_and_apoptosis_induction_in_rheumatoid_synovial_fibroblasts_and_monocytes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0896-8411(01)90542-6 DB - PRIME DP - Unbound Medicine ER -