5-hydroxytryptamine (5-HT) is involved in the stress-induced alteration of colonic functions, specifically motility and secretion, but its precise mechanisms of regulation remain unclear. In the present study, we have investigated the effects of 5-HT on rat colonic mucosal secretion after acute water immersion restraint stress, as well as the underlying mechanism of this phenomenon, using short circuit current recording (ISC), real-time polymerase chain reaction, Western blot analysis, and enzyme-linked immunosorbance assays. After 2 h of water immersion restraint stress, the baseline ISC and 5-HT-induced ISC responses of the colonic mucosa were significantly increased. Pretreatment with selective 5-HT4 receptor antagonist, SB204070, inhibited the 5-HT-induced colonic ISC response by 96 % in normal rats and 91.2 % in acute-stress rats. However, pretreatment with the selective antagonist of 5-HT3 receptor, MDL72222 or Y-25130, had no obvious effect on 5-HT-induced ISC responses under either set of conditions. Total protein expression of both the mucosal 5-HT3 receptors and the 5-HT4 receptors underwent no significant changes following acute stress. Both colonic basal cAMP levels and foskolin-induced ISC responses were significantly enhanced in acute stress rats. 5-HT significantly enhanced the intracellular cAMP level via 5-HT4 receptors in the colonic mucosa from both control and stressed animals, and 5-HT-induced cAMP increase in stressed rats was not more than that in control rats. Taken together, the present results indicate that acute water immersion restraint stress enhances colonic secretory responses to 5-HT in rats, a process in which increased cellular cAMP accumulation is involved., Y. Li, L. S. Li, X. L. Zhang, Y. Zhang, J. D. Xu, J. X. Zhu., and Obsahuje bibliografii
Apolipoprotein J (clusterin) is a component of high-density lipoproteins, the high level of which is reversely correlated with the risk of coronary heart disease. In addition, it exerts anti-inflammatory and anti-apoptotic effects on endothelial cells and inhibits smooth muscle cell migration and proliferation, indicating that it may play a protective role in cardiovascular disease. However, the exact mechanisms by which this occurs remain unclear. This study aimed to clarify these underlying protective mechanisms by researching the inhibitory effects of apolipoprotein J via the NOD-like receptor protein 3 pathway on the inflammation induced by cholesterol crystals in THP‑1 macrophages. In culture, THP-1 macrophages were infected with adenoviral vectors containing apolipoprotein J genes and subsequently treated with cholesterol crystals. The inflammatory cytokines interleukin‑1β, interleukin 18 and tumour necrosis factor α were quantitatively measured with ELISA kits. NOD-like receptor protein 3, cysteinyl aspartate specific proteinase 1 and interleukin 1β were evaluated by Western blot and PCR analysis. As a result, apolipoprotein J expression was found to remarkably decrease the levels of inflammatory cytokines, including tumour necrosis factor α, interleukin 18 and interleukin 1β, secreted by THP‑1 macrophages. It was also found capable of inhibiting the levels of NOD-like receptor protein 3, cysteinyl aspartate-specific proteinase 1 and interleukin 1β both at the protein and mRNA levels. In the current study, we revealed that over-expression of apolipoprotein J attenuated the inflammation induced by cholesterol crystals through inhibition of the NOD-like receptor protein 3 inflammasome pathway.