Tumor necrosis factor α-induced adipose-related protein expression in experimental arthritis and in rheumatoid arthritis

Inoue, Akira; Matsumoto, Isao; Tanaka, Yôko; Iwanami, Keiichi; Kanamori, Akira; Ochiai, Naoyuki; Goto, Daisuke; Ito, Satoshi; Sumida, Takayuki

doi:10.1186/ar2779

Cited by 30 publications

(43 citation statements)

References 21 publications

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“…STEAP4 was clearly detected in CD68 ? cells localizing lining layer in RA synovium; these results were consistent with our former study [7]. Control Ig (ctl Ig) did not stain samples (Fig.…”

Section: Steap4 Expression Is Linked To Tnfa In Ra Synoviumsupporting

confidence: 93%

“…We have previously reported a strong STEAP4 expression in CD68 ? cells from RA synovium [7], although overlapping expression of CD68 and a fibroblast marker was also observed [11,12]. FLS cells derived from patients with RA were positive for CD68 expression that overlapped with the expression of STEAP4 (Fig 2b).…”

Section: Steap4 Localization In Flsmentioning

confidence: 93%

“…Rabbit anti-STEAP4 antibodies (Abs) were prepared as described previously [7]. Briefly, a rabbit was immunized subcutaneously with STEAP4 peptide [3][4][5][6][7][8][9][10][11][12][13][14][15] (KTCIDALPLTMNS) in complete Freund's adjuvant (CFA). Serum was collected and loaded onto a protein A column for initial purification, before undergoing affinity purification using a STEAP4 peptide 3-15 column.…”

Section: Quantitative Pcrmentioning

confidence: 99%

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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

Tanaka¹,

Matsumoto²,

Iwanami³

et al. 2011

Mod Rheumatol

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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.

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Section: Steap4 Expression Is Linked To Tnfa In Ra Synoviumsupporting

confidence: 93%

Section: Steap4 Localization In Flsmentioning

confidence: 93%

Section: Quantitative Pcrmentioning

confidence: 99%

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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

Tanaka¹,

Matsumoto²,

Iwanami³

et al. 2011

Mod Rheumatol

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“…56-58). The colocalization of STEAP4 with CD68 þ in the joints of patients with rheumatoid arthritis and its overexpression in the synovia of patients with rheumatoid arthritis and osteoarthritis indicate the role of STEAP4 in these diseases (43). Still, further studies are required to support the involvement of STEAP4 in the inflammatory process in the joints of patients with rheumatoid arthritis.…”

Section: Steap4mentioning

confidence: 99%

“…STEAP4 has also been associated with obesity, insulin resistance, inflammation, and prostate cancer progression (11,(41)(42)(43)(44)(45). The STEAP4 mouse homolog, TNFa-induced adipose-related protein (TIARP), was first identified as a plasma membrane protein overexpressed in both white and brown adipose tissues, with increased expression during preadipocyte differentiation and strongly induced by TNF-a, interleukin-6 (IL-6), growth hormone, and interleukin-1b (IL-1b).…”

Section: Steap4mentioning

confidence: 99%

STEAP Proteins: From Structure to Applications in Cancer Therapy

Gomes

Maia²,

Santos³

2012

Molecular Cancer Research

171

214

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The human 6-transmembrane epithelial antigen of prostate (STEAP) family comprises STEAP1, STEAP2, STEAP3, and STEAP4. All of these proteins are unique to mammals and share an innate activity as metalloreductases, indicating their importance in metal metabolism. Overall, they participate in a wide range of biologic processes, such as molecular trafficking in the endocytic and exocytic pathways and control of cell proliferation and apoptosis. STEAP1 and STEAP2 are overexpressed in several types of human cancers, namely prostate, bladder, colon, pancreas, ovary, testis, breast, cervix, and Ewing sarcoma, but their clinical significance and role in cancer cells are not clear. Still, their localization in the cell membrane and differential expression in normal and cancer tissues make STEAP proteins potential candidates as biomarkers of several cancers, as well as potential targets for new immunotherapeutic strategies for disease attenuation or treatment. This review brings together the current knowledge about each STEAP protein, giving an overview of the roles of this family of proteins in human physiology and disease, and analyzes their potential as immunotherapeutic agents in cancer research. Mol Cancer Res; 10(5); 573-87. Ó2012 AACR. IntroductionThe 6-transmembrane epithelial antigen of prostate (STEAP) family of proteins includes 4 members, named 6-transmembrane epithelial antigen of prostate 1 to 4 (STEAP1-STEAP4). They all have in common a 6-transmembrane domain, a COOH-terminal domain with significant homology to the yeast FRE family of b-type cytochrome metalloreductases, and an N-terminal with homology to the archaeal and bacterial F 420 H 2 :NADP

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