Title of project : Mechanisms underlying angiotensin II-stimulated production of proinflammatory cytokines : Are transcription factors involved?

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We recently reported an involvement of angiotensin II(ANG II) and ANG type 1(AT1) receptor in the hepatic, splenic and brain expression of IL-1ss induced in rats by lipopolysaccharide(LPS). We investigated whether ANG II contributes to the IL-1 production through its effect on the activation of proinflammatory transcription factors, NF-κB and AP-1, induced in the rat's liver and spleen by LPS. Surprisingly, LPS induced a marked increase in the hepatic activation of NF-κB, an effect that was significantly enhanced (rather than reduced) by pre-treatment with the ACE inhibitor and AT1-receptor antagonist. Furthermore, the LPS-induced expression of splenic AP-1 was significantly augmented by pre-treatment with the AT1-receptor antagonist. The present results suggest that endogenous ANG II or AT1 receptor suppress the activation of the hepatic or splenic transcription factors in LPS-treated rats. Our results does not seem to support the idea that NF-κB and AP-1 play a key role in the ANG II-enhanced production of proinflammatory cytokines induced by LPS in rats.