Newberry R D, Stenson W F, Lorenz R G
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Nat Med. 1999 Aug;5(8):900-6. doi: 10.1038/11341.
Intestinal inflammatory diseases are mediated by dysregulated immune responses to undefined luminal antigens. Feeding hen egg-white lysozyme to mice expressing a transgenic T-cell receptor that recognizes hen egg-white lysozyme peptide 46-61 resulted in no intestinal pathology; however, simultaneous administration of cyclooxygenase-2 inhibitors and dietary hen egg-white lysozyme resulted in increased proliferation of lamina propria mononuclear cells and crypt epithelial cells, crypt expansion and villus blunting. Lamina propria mononuclear cells produce high levels of cyclooxygenase-2-dependent arachidonic acid metabolites, which act as immunomodulators in the immune response to dietary antigen. These findings establish that cyclooxygenase-2-dependent arachidonic acid metabolites are essential in the development and maintenance of intestinal immune homeostasis.
肠道炎症性疾病是由对不明腔抗原的免疫反应失调介导的。给表达识别鸡卵清溶菌酶肽46 - 61的转基因T细胞受体的小鼠喂食鸡卵清溶菌酶，未导致肠道病理变化；然而，同时给予环氧化酶-2抑制剂和日粮鸡卵清溶菌酶会导致固有层单核细胞和隐窝上皮细胞增殖增加、隐窝扩张和绒毛变钝。固有层单核细胞产生高水平的环氧化酶-2依赖性花生四烯酸代谢产物，这些代谢产物在对日粮抗原的免疫反应中作为免疫调节剂。这些发现表明，环氧化酶-2依赖性花生四烯酸代谢产物在肠道免疫稳态的发展和维持中至关重要。
