Are transcription factors NF-kappaB and AP-1 involved in the ANG II-stimulated production of proinflammatory cytokines induced by LPS in dehydrated rats?
We recently reported an involvement of ANG II and the ANG II type 1 (AT1) receptor in the hepatic expression of IL-1beta induced in dehydrated rats by LPS. Here, we first confirmed that ANG II and AT1 receptors contribute to the LPS-induced increase in the splenic concentration of IL-1beta in dehydrated rats. We then investigated whether ANG II contributes to IL-1 production through a modulating effect on the activation of proinflammatory transcription factors (NF-kappaB and AP-1) that is induced in the dehydrated rat's liver and spleen by intravenous injection of LPS. Surprisingly, LPS markedly increased the hepatic activation of NF-kappaB, an effect that was significantly enhanced (rather than reduced) by pretreatment with an ANG-converting-enzyme (ACE) inhibitor or AT1-receptor antagonist. Furthermore, the same ACE inhibitor and AT1-receptor antagonist each increased the resting NF-kappaB activity in the liver and spleen, although they had no effect on the LPS-induced splenic expression of NF-kappaB. Both hepatic and splenic AP-1 expressions were enhanced by LPS. This response was significantly augmented by pretreatment with the AT1-receptor antagonist (but not with the ACE inhibitor) in the spleen, while in the liver, neither drug had any effect. These results suggest that the endogenous ANG II or AT1 receptor suppresses the activation of hepatic or splenic transcription factors in dehydrated rats given LPS. Our results seem not to support the idea that NF-kappaB and AP-1 play key roles in the ANG II-induced enhancement of the production of proinflammatory cytokines that is induced by LPS in dehydrated rats.
Sasaki
Kumiko
K
Div. of Integrative Physiology, Dept. of Functional, Morphological, and Regulatory Science, Tottori Univ., Faculty of Medicine, Yonago, Tottori 683, Japan.
Taniguchi
Makoto
M
Miyoshi
Michio
M
Goto
Osamu
O
Sato
Kenzo
K
Watanabe
Tatsuo
T
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D003681:Dehydration / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D000804:Angiotensin II