title: The conversion of redox status of peritoneal macrophages during pathological progression of spontaneous inflammatory bowel disease in Janus family tyrosine kinase 3(-/-) and IL-2 receptor gamma(-/-) mice.
abstract: The distinct thiol redox status in macrophages, either elevated or reduced intracellular content of glutathione (GSH), was confirmed during aging in IL-2 receptor (IL-2R)gamma and Janus family tyrosine kinase (JAK)3 gene-disrupted mice. Oxidative macrophages (OMp) with reduced GSH dominated initially at a younger age in both mice. OMp-dominated JAK3 or IL-2R gamma chain-deficient mice showed shortened life longevity compared with wild-type littermates. These mice elicited spontaneous onsets of inflammatory bowel disease (IBD)-like symptoms accompanied with the conversion of the redox status of macrophages to reductive phenotypes with elevated intracellular GSH. Conversion of OMp to the reductive phenotype by GSH monoethyl ester or by a beta-(1-3)-glucan accelerated the disease onset, concomitant with the skewing from T(h)2 to T(h)1 responses. On the contrary, N,N'-diacetyl cystine dimethylester, which is capable of inducing OMp, delayed the incidence of IBD-like symptoms and improved the survival rate. This implies that the conversion of OMp/T(h)2 to reductive macrophages/T(h)1 may be critical for the disease progression. The study of these mice may provide insight into the mechanisms underlying Crohn's disease and ulcerative colitis.
authors.affiliation: Basic Research Laboratories, Ajinomoto Co. Inc., 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki 210-0861, Japan.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Murata
authors.forename: Akira
authors.initials: A
authors.lastname: Yamashita
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sugamura
authors.forename: Junji
authors.initials: J
authors.lastname: Hamuro
mesh_terms: D000818:Animals; D016207:Cytokines / Q000494:pharmacology; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D015212:Inflammatory Bowel Diseases / Q000209:etiology / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D053616:Janus Kinase 3; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000172:deficiency* / Q000235:genetics; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D016207:Cytokines; D015375:Receptors, Interleukin-2; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3; D005978:Glutathione