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ERK2 and JNK1 contribute to TNF-?-induced IL-8 expression in synovial fibroblasts.


ABSTRACT: Tumor necrosis factor ? (TNF-?) induces the expression and secretion of interleukin 8 (IL-8), which contributes to synovitis in rheumatoid arthritis (RA). To elucidate the mechanism of the onset of RA, we used synovial fibroblasts without autoimmune inflammatory diseases and investigated MAPK signaling pathways in TNF-?-induced IL-8 expression. Synovial fibroblasts isolated from healthy dogs were characterized by flow cytometry, which were positive for the fibroblast markers CD29, CD44, and CD90 but negative for the hematopoietic cell markers CD14, CD34, CD45, and HLA-DR. TNF-? stimulated the secretion and mRNA expression of IL-8 in a time- and dose-dependent manner. ERK and JNK inhibitors attenuated TNF-?-induced IL-8 expression and secretion. TNF-? induced the phosphorylation of ERK1/2 and JNK1/2. TNF-?-induced IL-8 expression was attenuated both in ERK2- and JNK1-knockdown cells. TNF-?-induced ERK1/2 or JNK1/2 was observed in ERK2- or JNK1-knockdown cells, respectively, showing that there is no crosstalk between ERK2 and JNK1 pathways. These observations indicate that the individual activation of ERK2 and JNK1 pathways contributes to TNF-?-induced IL-8 expression in synovial fibroblasts, which appears to be involved in the progress in RA.

SUBMITTER: Namba S 

PROVIDER: S-EPMC5555573 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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ERK2 and JNK1 contribute to TNF-α-induced IL-8 expression in synovial fibroblasts.

Namba Shinichi S   Nakano Rei R   Kitanaka Taku T   Kitanaka Nanako N   Nakayama Tomohiro T   Sugiya Hiroshi H  

PloS one 20170814 8


Tumor necrosis factor α (TNF-α) induces the expression and secretion of interleukin 8 (IL-8), which contributes to synovitis in rheumatoid arthritis (RA). To elucidate the mechanism of the onset of RA, we used synovial fibroblasts without autoimmune inflammatory diseases and investigated MAPK signaling pathways in TNF-α-induced IL-8 expression. Synovial fibroblasts isolated from healthy dogs were characterized by flow cytometry, which were positive for the fibroblast markers CD29, CD44, and CD90  ...[more]

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