Analysis of the effect of stress on the gut-associated immune systems by the genetic method

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It is reported that stress is deeply concerned with the development of intestinal diseases, such as large intestine cancer, an inflammational bawel disease, and irritable colon syndrome. Therefore, we investigated the effect of the isolation stress on the gut-associated lymphoid system. ConA responses of mesenteric lymph node cells were reinforced at the acute phase of the stress, and was suppressed at the chronic phase. T/B ratio was enhanced at the acute phase, and suppressed at the chronic phase. The production of IL-4 was markedly enhanced at the chronic phase, showing the possibility of Th2 type-dominant. Thus, the mesenteric lymph node cells were notably influenced by the stress, though the spleen cells exhibited the inverse relationship. Serum cortisone levels were upregulated in acute phase, while substance P levels were upregulated in chronic phase.The influence of stress on the large intestine was analyzed in the gene discovery analysis using DNA array. Gene's upregulated sig … More nificantly compared to control were most abundant in chronic phase. Reduction of IL- 12 production and upregulation of IL- 10 and its receptor suggested that the stress changes the Th1/Th2 balance to Th2. In the sample from 2 and 30 day isolation, many genes related to hormone, neurotransmitter, and their receptors were upregulated. These results indicated that isolation stress profoundly affects the large intestine, and made it to the neuronal hypersensitivity.Next experiments were performed using chronic ulcerative colitis-induced mice by trinitrochlorobenzene (TNBS) under isolation stress load for 30 days or not. RNA was extracted from the large intestines and gene expression analysis was performed. As a result, the transcription factor & DNA-binding proteins related genes were upregulated in TNBS treated mice. The ion channels & transport proteins related genes were upregulated in mice treated with TNBS and loaded with stress. Thus, stress increases and modulates gene expression in large intestine. These results were ascertained by RT-PCR using the real-time PCR. Less