International Immunology, Vol. 14, No. 6, pp. 627-636,
June 2002
© 2002 Japanese Society for Immunology
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 
–/– mice
1 Basic Research Laboratories, Ajinomoto Co. Inc., 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki 210-0861, Japan 2 Department of Anatomy, Hamamatsu Medical University, Hamamatsu 431-3192, Japan 3 Division of Molecular Genetics, Chiba University School of Medicine, Chiba 263-8522, Japan 4 Department of Immunology, Tohoku University School of Medicine, Sendai 980-8575, Japan
Correspondence to: J. Hamuro; E-mail: junji_hamuro{at}ajinomoto.com
Transmitting editor: M. Miyasaka
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)
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 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 ß-(1–3)-glucan accelerated the disease onset, concomitant with the skewing from Th2 to Th1 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/Th2 to reductive macrophages/Th1 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.
Keywords: glutathione, IL-2 receptor , inflammatory bowel disease, innate immunity, JAK3, reductive and oxidative macrophages
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