“…Three proinflammatory cytokines are known to downregulate NKA: IFN-␥, TNF-␣, and IL-1. T cell-produced IFN-␥ (18,93,134) is thought to activate the PKC downstream STAT1 phosphorylation and Raf-1, MEK, ERK2, and p38 MAPK (92), but there is conflicting evidence regarding its dependency of NO (134,158). TNF-␣ decreases the NKA activity possibly through PGE 2 (95,100) and to a smaller extent also lowers the expression of the Na/K/Cl symporter (95), whereas IL-1 downregulates NKA but stimulates Na/K/Cl symporter (and thus Cl Ϫ secretion) (76).…”