p38β MAP kinase protects rat mesangial cells from TNF‐α‐induced apoptosis

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Abstract
P38 MAP kinases (p38) and c‐Jun N‐terminal protein kinases (JNK) have been associated with TNF‐α‐induced apoptosis. However, recent studies indicate that an early but brief activation of JNK and/or p38 may actually protect some cells from TNF‐α‐induced apoptosis. Whether the activation of JNK and p38 provides a pro‐ or anti‐apoptotic signal for TNF‐α has been controversial. In this study, we investigated the role of p38 in the regulation of TNF‐α cytotoxicity in rat mesangial cells. Treatment of the cells with TNF‐α alone had little effect on their viability, but they became very sensitive to apoptosis when treated with TNF‐α in the presence of the p38 inhibitor SB 203580. These results suggested that the p38 pathway is critical for mesangial cells to survive the toxic effect of TNF‐α. Using adenovirus‐mediated gene transfer technique, we further demonstrated that p38β, but not p38α, is essential to protect the cells from TNF‐α toxicity. It has been speculated that there is a synergetic interaction between the p38 and the nuclear factor‐κB (NF‐κB) pathways in protecting certain cells from apoptosis. However, expression of neither p38β nor its dominant negative mutant in mesangial cells interfered with TNF‐α‐induced translocation of NF‐κB, the initial step of NF‐κB activation. While it is unclear whether p38β regulates NF‐κB transcription activity at other steps, it is apparent that p38β does not affect TNF‐α‐induced NF‐κB activation at the stage of nuclear translocation. J. Cell. Biochem. 82: 556–565, 2001.