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TIS21 inhibits interleukin 6 (IL-6) expression via suppression of STAT3 activation in normal fibroblast cell

Linh, Nguyen Quy; Lim, In Kyoung; Park, Tae Jun
Department of Biochemistry & Molecular Biology, Ajou University School of Medicine
Interleukin 6 (IL-6) acts as a pro-inflammatory cytokine. IL-6 has important roles in cancer process, especially in cell proliferation. There are several reports which show that JAK/STAT3 signaling pathway can regulate IL-6 expression. STAT3 could be activated by Chk2 during DNA damage and senescence. TIS21 (12-o-tetradecanoyl-phorbol-13-acetate (TPA)-inducible sequence 21), ortholog of human B-cell translocation gene 2 (BTG2) is a tumor suppressor gene and down-regulated in various cancers. We hypothesized that TIS21 can down-regulate IL-6 expression via inhibition of STAT3 pathway. In this study, we show that IL-6 expression increases more than 2 fold in response to Chk2 overexpression in human diploid fibroblast (HDF) cell. At the mechanistic level, Chk2 up regulates IL-6 expression at mRNA level by activating STAT3 pathway. We also observed that TIS21 inhibited IL-6 expression and down-regulated the levels of p-STAT3 and p-Chk2. Taking together, our results suggest that TIS21 has a role in IL-6 expression at mRNA level via down-regulation of Chk2, inhibiting Chk2 – STAT3 signaling pathway. The data exhibits anti-carcinogenic potential of TIS21 via down-regulation of IL-6 in HDF cell. However, the detail mechanism of this interplay is underway.
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