RRC ID 11910
Author Tanaka Y, Matsumoto I, Iwanami K, Inoue A, Minami R, Umeda N, Kanamori A, Ochiai N, Miyazawa K, Sugihara M, Hayashi T, Goto D, Ito S, Sumida T.
Title Six-transmembrane epithelial antigen of prostate4 (STEAP4) is a tumor necrosis factor alpha-induced protein that regulates IL-6, IL-8, and cell proliferation in synovium from patients with rheumatoid arthritis.
Journal Mod Rheumatol
Abstract Human six-transmembrane epithelial antigen of prostate4 (STEAP4), an ortholog of mouse tumor necrosis factor-α-induced adipose-related protein (TIARP), plays a role in tumor necrosis factor (TNF)-dependent arthritis models. However, its role in rheumatoid arthritis (RA) is still obscure. This study explored such a role for STEAP4. The expressions of STEAP4, TNFα, and IL-6 were compared in synovia of RA and osteoarthritis patients. STEAP4 induction was examined in TNFα-stimulated fibroblast-like synoviocytes (FLS) in vitro. FLS (with/without TNFα stimulation) were also analyzed for IL-6 expression after STEAP4 knockdown, using siRNA or transfection with STEAP4-plasmid DNA. IL-8, cell proliferation, and apoptosis were also evaluated in STEAP4-overexpressing FLS. The expression of STEAP4 in joints correlated with TNFα expression, specifically in RA synovium. In the cultured FLS, STEAP4 protein expression was augmented by TNFα activation, and localized in endosomal/lysosomal compartments. STEAP4 downregulation by siRNA enhanced the expression of IL-6 mRNA, while STEAP4 overexpression suppressed IL-6 and IL-8 expression, inhibited cell proliferation, and induced apoptosis via caspase-3. The results indicated that human STEAP4 is regulated by TNFα in synovium, where it controls IL-6 secretion and proliferation of FLS, suggesting that STEAP4 might potentially suppress the pathogenesis of TNFα-induced arthritis such as RA.
Volume 22(1)
Pages 128-36
Published 2012-2-1
DOI 10.1007/s10165-011-0475-y
PMID 21633911
MeSH Arthritis, Rheumatoid / genetics Arthritis, Rheumatoid / metabolism* Arthritis, Rheumatoid / pathology Cell Proliferation / drug effects Fibroblasts / drug effects Fibroblasts / metabolism Fibroblasts / pathology Gene Expression / drug effects Gene Silencing Humans Interleukin-6 / metabolism* Interleukin-8 / metabolism* Jurkat Cells Membrane Proteins / genetics Membrane Proteins / metabolism* Osteoarthritis, Knee / metabolism Osteoarthritis, Knee / pathology Oxidoreductases / genetics Oxidoreductases / metabolism* RNA, Small Interfering / genetics RNA, Small Interfering / pharmacology Synovial Membrane / drug effects Synovial Membrane / metabolism* Synovial Membrane / pathology Transfection Tumor Necrosis Factor-alpha / genetics Tumor Necrosis Factor-alpha / metabolism Tumor Necrosis Factor-alpha / pharmacology
IF 1.973
Times Cited 21
Human and Animal Cells MH7A and Jurkat cell lines