| 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
|
|
WOS Category
|
RHEUMATOLOGY
|
| Resource |
| Human and Animal Cells |
MH7A and Jurkat cell lines |
