BackgroundIrritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder. Post-infectious IBS (PI-IBS) is caused by an acute gastrointestinal infection preceding the onset of symptoms. However, the pathophysiology of PI-IBS is not clear, and the purpose of this study was to investigate the probable immune mechanisms of PI-IBS.MethodsC57BL/6 mice were randomly assigned to either an infection group or a control group. Mice in the infection group were infected with Trichinella spiralis to establish a model of PI-IBS (500 Trichinella), while control mice received only salt solution. Visceral sensitivity of colorectal distention in mice was evaluated by abdominal withdrawal reflex scores and intestinal inflammation was assessed using hematoxylin-eosin staining; at day 56 post-infection, the mRNA and protein levels of specific cytokines in the gut segments were detected using reverse-transcription polymerase chain reaction and enzyme-linked immunoabsorbent assay.ResultsLevels of interferon γ and interleukin (IL)-17 in the PI-IBS group were significantly increased in the duodenum and ileum, and IL-10 was decreased in the jejunum, ileum, and colon compared with control mice. However, the expression level of IL-1β was not significantly different between the two groups.ConclusionsThe present study suggests that the local low-grade inflammation and immune activation that are an important component of the pathophysiology of PI-IBS are primarily induced and maintained by specific cytokines.

Our previous studies indicated that cyclooxygenase-2 inhibitor or octreotide could suppress the proliferation of gastric adenocarcinoma in vitro or in vivo. The present study was aimed to find whether rofecoxib combined with octreotide could enhance the inhibitive effects on the growth of gastric cancer. The effect of rofecoxib or octreotide on proliferation of gastric cancer cell line was determined by 3 H-thymidine ribotide incorporation. The TdT-mediated dUTP nick endlabeling assay was used to detect the apopotosis. To determine their synergic antineoplastic effects, the interaction between rofecoxib and octreotide on SGC-7901 cell was evaluated by the median effect plot. After orthotopical implantion of xenografts of human gastric cancer in stomach, nude mice were given rofecoxib plus octreotide for 8 weeks. Cyclooxygenase-2 in gastric cancer tissues was measured by immunohistochemistry. Combination of rofecoxib and octreotide presented synergistic effect (combination index < 1) in the majority of responses. The inhibitory rate for xenografts in nude mice was 89.7% in rofecoxib group. Combination of rofecoxib and octreotide enhanced inhibitory rate to 98.8%. The combination greatly increased the apoptotic index (78.20% ؎ 6.45%) of the xenografts as compared with that of using rofecoxib alone (46.60% ؎ 3.42%); the difference was very significant (p < 0.001). Rofecoxib could inhibit the activity of cyclooxygenase-2 in the tissue of gastric adenocarcinomas of nude mice. Our results indicate that combination of rofecoxib and octreotide significantly enhances the antiproliferative effect in gastric adenocarcinoma, which might have potential therapeutic value. © 2004 Wiley-Liss, Inc. Key words: rofecoxib; octreotide; gastric adenocarcinoma; cyclooxygenase-2The poor prognosis of unresectable gastric adenocarcinoma and the various disappointing therapeutic modalities make further investigation of new therapeutic approach for advanced gastric cancer of primary importance. Accumulative evidence has shown that overexpression of cyclooxygenase-2 (COX-2) in gastric adenocarcinoma might play a crucial role in invasive tumor growth and offer a new strategy against cancer by the use of COX-2 inhibitors. [1][2][3][4] The inhibitive effect of aspirin or rofecoxib, a higher selective COX-2 inhibitor 5 on the proliferation of gastric cancer, has been observed in our previous studies. 6,7 Various studies have demonstrated that the growth of normal cells and malignant tumor may be regulated by gut peptides. 8,9 In the stomach, besides the known inhibitory function of somatostatin (SST) on acid secretion, it has been suggested that the analogues of SST could be candidates for arresting the growth of gastric adenocarcinoma. Previous data from the literature have shown that the mean tumor volume in nude mice treated with octreotide, an analogue of SST, was significantly lower than that of control group with an inhibitory rate of 60.6%. 6,10 The antineoplastic action of octreotide is thought to be mediated through the receptors for S...

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This study aimed to investigate the protective effects of preinduction of heat shock protein 70 (HSP70) on Trichinella spiralis infection-induced post-infectious irritable bowel syndrome (PI-IBS) in mice. Trichinella spiralis infection significantly reduced HSP70 abundance, ileal villus height and crypt depth, expression of tight junctions, serum lysine and arginine concentrations, and ileal SCL7A6 and SCL7A7 mRNA levels, induced inflammatory response, and activated NF-κB signaling pathway. Meanwhile, the heat treatment upregulated HSP70 expression, and then reversed intestinal dysfunction and inflammatory response. Preinduction of HSP70 enhanced serum arginine and intestinal SCL7A7 expression and inhibited NF-κB activation compared with PI-IBS model. Treatment with pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor) and N-nitro-L-arginine methyl ester hydrochloride (L-NAME, a nitric oxide synthase inhibitor, NOS) further demonstrated that preinduction of HSP70 might inhibit NF-κB and activated NOS/nitric oxide (NO) signaling pathways. In conclusion, preinduction of HSP70 by heat treatment may confer beneficial effects on Trichinella spiralis infection-induced PI-IBS in mice, and the protective effect of HSP70 may be associated with inhibition of NF-κB and stimulation of NOS/NO signaling pathways.

The interstitial cells of Cajal (ICC) are basic components of gastrointestinal motility. However, changes in ICC and their role in post‑infection irritable bowel syndrome (PI‑IBS) remain to be elucidated. To observe the impact of alterations in the ICC on intestinal motility in a PI‑IBS mouse model, female C57BL\6 mice were infected by the oral administration of 400 Trichinella spiralis larvae. The abdominal withdrawal reflex, intestine transportation time (ITT), grain numbers, Bristol scores, wet/dry weights and the percentage water content of the mice feces every 2 h were used to assess changes in the intestinal motor function. The intestines were excised and sectioned for pathological and histochemical examination. These intestines were also used to quantify the protein and mRNA expression of c‑kit. The C57BL\6 mouse can act as a PI‑IBS model at day 56 post‑infection. Compared with the control mice, the ITT was shorter, the grain numbers, Bristol scores, wet weights and water contents of the mice feces were higher and the dry weights were unchanged in the PI‑IBS mice. The protein and mRNA expression levels of c‑kit were upregulated in the entire PI‑IBS mouse intestines. Following immunohistochemical staining, the increased number of c‑kit‑positive cells were detected predominantly in the submucosa and myenteron. These results suggested that the alterations of the ICC resulted in the changes of the intestinal motility patterns in the PI‑IBS mouse models induced by Trichinella spiralis infection, which may be the main mechanism underlying intestinal motility disorders in PI‑IBS.