CCK-8 INHIBITS LPS-INDUCED IL-1?? PRODUCTION IN PULMONARY INTERSTITIAL MACROPHAGES BY MODULATING PKA, P38, AND NF-??B PATHWAY

• DOI: 10.1097/shk.0b013e3180ze26dd
• Publication Date: 2007-05-11T08:13:49Z
• Authors: Shujin Li; Zhiyu Ni; Bin Cong; Weijuan Gao; Shunjiang Xu; Chunyan Wang; Yuxia Yao; Chunling Ma; Yiling Ling
• Keywords: Proinflammatory cytokine; Cyclic adenosine monophosphate

The neuropeptide cholecystokinin octapeptide (CCK-8) inhibits inflammation by downregulating the expression of proinflammatory cytokines, such as tumor necrosis factor alpha and interleukin (IL) 1beta during endotoxin shock. However, signaling mechanism CCK-8 action has not yet been clearly elucidated. In this study, we have examined possible pathways which lipopolysaccharide (LPS)-induced IL-1beta production in rat pulmonary interstitial macrophages. macrophages, LPS is known to activate p38 kinase, which, turn, activates nuclear (NF)-kappaB induce production. We found that pretreatment cells with blocked LPS-induced NF-kappaB activation, Furthermore, treatment activated cyclic adenosine monophosphate-protein kinase A pathway H-89 (a protein inhibitor), abrogated inhibitory effects on activation activation. addition, also demonstrate specific antagonist CCK-1 receptor (CCK-1R) CCK-2 (CCK-2R) abrogate CCK action, CCK-1R more significant. These results suggest these responses were mediated through CCK-2R, might be major responsible for anti-inflammatory effect CCK-8. Taken together, our indicate stimulation CCK-2R block