| It is well known that inflammatory response is a kind of protective stress for organism to resist the attack of external etiological factors. Excessive activated immune cells produce and release large quantity of various pro-inflammatory cytokines including TNF-α, IL-1, IL-6 and so on. Overproduction of the cytokines can induce cascade reaction of inflammatory mediators by autocrine and paracrine, which result in uncontrolled disturbance of organisms, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS).Among infectious and non-infectious factors, which stimulate the host inflammatory cells to produce large quantity of cytokines and inflammatory mediators, endotoxin (lipololysaccharide, LPS), the main outer membrane component of Gram-negative bacteria, is the most potent and plays a key role during severe Gram-negative infection, sepsis and septic shock.In the pathological process of SIRS and MODS, the lung is a high sensitive target organ to pathogenic factors to be dysfunctional, and an important drive organ of MODS. The inflammatory cells are activated and accumulated in the lung to produce cytokines, which induce or facilitate local and systemic inflammatory response, mediate tissue damage, promote the MODS generation and development. Macrophages are the critical effector cells, which produce and release many kinds of inflammatory mediators and induce inflammatory response. Pulmonary macrophages consist of alveolar macrophages (AMs), pulmonary interstitial macrophages (PIMs), pulmonary intravascular macrophages, pleural macrophages, dendritic cell and so on. Among them, PIMs, to which are paid close attention recently, play a pivotal role in inducing inflammatory response. The same as AMs, PIMs also have the ability of phagocytosis and release various inflammatory mediators, especially have the strong ability to secret IL-1 and IL-6. It was reported that there was a significant increase in production of oxygen free radicals from PIMs, but not from AMs in the rats treated with LPS. The treatment also markedly enhanced phagocytosis only in PIMs and caused a significant increase in chemotaxis toward C5a in PIMs. These data demonstrate that PIMs play an important role in the inflammatory response of the lungs in endotoxemia. Cholecyetokinin (CCK), a typical braingut peptide, is discovered initially in the gut as a gastrointestinal hormone with the function of contracting gallbladder and mediating pancreatic secretion, and subsequently localized in the central and peripheral nervous system as a neurotransmitter or neuromodulator to play a pivotal role. Recent years, a series of studies showed that CCK-8 had the effect of anti-inflammation. A lot of data demonstrate that CCK-8 causes an in vitro inhibition of LPS-induced NF-κB activity and mCD14 expression in rat PIMs. Consistently, the production of pro- inflammatory cytokines including TNF-α, IL-1β and IL-6 in endotoxin shock (ES) rat was also inhibited by CCK-8 in vivo. These results suggested that CCK-8 has anti-inflammatory effect to some extent, which was also confirmed by a morphological observation that CCK-8 clearly lessened the leukocytic infiltrate and capillary silt in lung, spleen, kidney and myocardium tissues in ES rat. Series studies show the fine prospects of the CCK-8's anti-inflammation effects. However, the mechanisms of receptor and anti-inflammatory signal transduction activated by CCK-8 remain unclear. As we all know, CCK-8 exerts anti-inflammation effect through its receptors in target cell. More recently, some studies of our laboratory suggested the presence of CCK-AR and CCK-BR mRNA expression in rat spleen cells, lung and heart tissues, and the expression could be up-regulated by LPS obviously, indicating that CCK-8 might bind to CCK receptors and interfere with the over activation of immune cells induced by LPS to exert its anti-inflammatory effect during endotoximia. The expression subtypes and binding characteristics of CCK receptors in PIMs and the upstream signaling mechanisms of...
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