Whereas under isotonic conditions inhibition of p38 boosted TNF secretion by enhancing SM-induced JNK1/2 and ERK1/2 phosphorylation,32 p38 inhibition under hypertonic conditions blunted NFAT5 activation and transcription of its target gene TNF.26, 27, 34 Activation of an additional endogenous TNF-producing pathway might be of special relevance in tumor cells that respond poorly to SM alone. This evidence concerns the gene MAPK8 and neoplasm.