Stress activated protein kinase p38 is involved in IL-6 induced transcriptional activation of STAT3

The acute phase protein expression In HepG2 human hepatoma cells and promot es the growth of mouse B9 hybridoma. The signaling cascades leading to thes e biological functions are only partially known. We analysed the involvemen t of MAPK homologues in IL-6 transduction pathways and found that interleuk in-6 triggered activation of p38 stress-activated protein kinase (p38) but not of jun kinase. p38 activity was required for biological functions inclu ding acute phase protein secretion from HepG2 hepatoma and proliferation of B9 hybridoma cells. Using a reporter gene construct containing a 190 bp pr omoter fragment of the acute phase protein haptoglobin we found that p38 is involved in transcriptional activation of the haptoglobin promoter by STAT 3 but not by NF-IL6. Thus, we present evidence for a role of p38 in IL-6 in duced functions and a possible cross-talk between this MAPK homologue and t he STAT pathway.