Heat shock protein 20 (HSPB6) regulates TNF-α-induced intracellular signaling pathway in human hepatocellular carcinoma cells

We previously demonstrated that the expression of HSP20, a small heat shock protein, is inversely correlated with the progression of HCC. Inflammation is associated with HCC, and numerous cytokines, including TNF-alpha, act as key mediators in the progression of HCC. In the present study, we investigated whether HSP20 is implicated in the TNF-alpha-stimulated intracellular signaling in HCC using human HCC-derived HuH7 cells in the presence of TNF-alpha. In HSP20-overexpressing HCC cells, the cell growth was retarded compared with that in the control cells under long-term exposure of TNF-alpha. Because NF-kappa B pathway is the main intracellular signaling system activated by TNF-alpha, we investigated the effects of HSP20-overexpression of this pathway. The protein levels of but not IKK-beta, in the HSP20-overexpressing cells were decreased. Short-term exposure to TNF-alpha-induced phosphorylation and degradation of 1 kappa B, and the phosphorylation and transactivational activity of NF-kappa B were suppressed in the HSP20-overexpressing HCC cells. Furthermore, the increase in IKK-alpha levels was accompanied by a decrease in the HSP20 levels in human HCC tissues. These findings strongly suggest that HSP20 might decrease the IKK-alpha protein level and that it down-regulates the TNF-alpha-stimulated intracellular signaling in HCC, thus resulting in the suppression of HCC progression. (C) 2014 Elsevier Inc. All rights reserved.