Journal
SHOCK
Volume 27, Issue 6, Pages 678-686Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/shk.0b013e3180ze26dd
Keywords
monocytes/macrophages; lipopolysaccharide; cholecystokinin; interleukin 1 beta; signal transduction
Ask authors/readers for more resources
The neuropeptide cholecystokinin octapeptide (CCK-8) inhibits inflammation by downregulating the expression of proinflammatory cytokines, such as tumor necrosis factor alpha and interleukin (IL) 1 beta during endotoxin shock. However, the signaling mechanism of CCK-8 action has not yet been clearly elucidated. In this study, we have examined the possible signaling pathways by which CCK-8 inhibits lipopolysaccharide (LPS)-induced IL-1 beta production in rat pulmonary interstitial macrophages. In macrophages, LPS is known to activate p38 kinase, which, in turn, activates nuclear factor (NF)-kappa B to induce IL-1 beta production. We found that the pretreatment of cells with CCK-8 blocked the LPS-induced p38 kinase, NF-kappa B activation, and IL-1 beta production. Furthermore, CCK-8 treatment activated the cyclic adenosine monophosphate-protein kinase A signaling pathway and H-89 (a protein kinase A inhibitor), abrogated the inhibitory effects of CCK-8 on p38 kinase activation and NF-kappa B activation. In addition, we also demonstrate that the specific antagonits to CCK-1 receptor (CCK-1R) and CCK-2 receptor (CCK-2R) abrogate the CCK action, and that the effects of the antagonits specific to CCK-1R is more significant. These results suggest that these responses were mediated through CCK-1R and CCK-2R, and CCK-1R might be the major receptor responsible for the anti-inflammatory effect of CCK-8. Taken together, our results indicate that the stimulation of cyclic adenosine monophosphate-protein kinase A signaling pathway by CCK-8 through CCK-1R and CCK-2R inhibits the LPS-induced activation of p38 kinase and NF-kappa B to block the IL-1 beta production in rat pulmonary interstitial macrophages.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available