| Co-Investigator(Kenkyū-buntansha) |
SHINODA Masataka SCHOOL OF MEDICINE,STAFF, 医学部, 医員
ANDO Takafumi SCHOOL OF MEDICINE,STAFF, 医学部, 医員
INA Kenji SCHOOL OF MEDICINE,STAFF, 医学部, 医員
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| Research Abstract |
An infiltration of immune and inflammatory cells, such as macrophages, T-cells, and B-cells, in the affected intestine makes the main pathological features of inflammatory bowel disease (IBD). Recruitment and activation of immune cells may be accelerated by release of immunoregulatory and chemotactic cytokines. The levels of immunoregulatory cytokines, such as interleukin(IL)-2 have been the subject of conflicting reports, probably because of consistently lower activity in the intestinal mucosa. Recently IL-7 and IL-15, which utilize common gamma-chains of IL-2 receptor, have been reported to exert many of the immunological activities on immune cells previously described for IL-2. Therefore, we examined the concentrations of IL-15, IL-7, and IL-2 in the organ cultures of intestinal mucosal tissues obtained from controls and patients with ulcerative colitis or Crohn's disease. IL-7 activity was detected only in 6 of total 100 cultures and IL-2 activity was totally absent in cultures of
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all patients group. In contrast, measurable levels of IL-15 were detected in all organ cultures with higher concentrations in IBD.In situ hybridization showed a localization of IL-15 messenger RNA to epithelial cells and infiltrating mononuclear cells, in which the signal was observed more diffusely in IBD specimens. Functionally, recombinant (r)IL-15 induced a dose-dependent increase in proliferative response and lymphokine activated-killer cell activity in both IBD and control lamina propria mononuclear cells (LPMC). Even more, rIL-15 was capable of inducing TNF-alpha and IFN-gamma production in LPMC, thus suggesting that IL-15 is an important cytokine in immune activation of mucosal immune cells in the intestinal mucosa with IBD.
Tissue accumulation of polymorphonuclear neutrophils (PMN) is another characteristic feature in the mucosal lesion of IBD.Increased mucosal production of IL-8 was observed in patients with IBD.Elevated levels of IL-8 may be involved in migration of PMN from the vascular space into the affected intestine and adhesion to the extracellular matrix. Moreover, mucosal specimens obtained from IBD patients exhibited higher levels of granulocyte colony-stimulating factor activity, thus providing possible mechanisms for tissues accumulation of PMN in IBD through inhibition of their apoptotic process. Less
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