I received my Ph.D. degree in 2002 from Tohoku University School of Medicine, working on immune cells redistribution after physical stress (i.e. exercise). Inflammatory cytokines and stress hormones increase after stress, and these cytokines and hormones increase leukocyte trafficking by regulating the expression of chemokine receptors and adhesion molecules on the surface of immune cells. This is one of the mechanisms for immune cell redistribution after stress.

Interestingly, inflammatory cytokines and stress hormones, suc as TNF-α and glucocorticoid, regulate not only immune cell distribution but also skeletal muscle mass. We have recently shown that oxidative skeletal muscles are more resistant than glycolytic muscles to cachexia caused by chronic heart failure and other chronic diseases, and injection of endotoxin in mice resulted in higher level of reactive oxygen species (ROS) and greater expression of atrogin-1 and MuRF1, in glycolytic muscle than in oxidative muscle. On the contrary, nitric oxide (NO) production, inducible NO synthase (iNos) and antioxidant gene expression were greatly enhanced in oxidative, but not in glycolytic muscles. NO donors enhanced iNos and antioxidant gene expression and blocked cytokine/endotoxin-induced atrogin-1 expression in cultured myoblasts and in skeletal muscle in vivo, suggesting that NO mediates protection against muscle wasting.

Currently, I am working on two main projects: 1) Molecular mechanisms of cachectic factor-induced skeletal muscle atrophy; and 2) Molecular mechanisms of NO-dependent protection of skeletal muscle atrophy. My research goal is to improve understanding of the relationships of cachectic factors and skeletal muscle atrophy.

Mitsuharu Okutsu , Ph.D.
Post-doctoral Fellow

Phone: (434)982-4473, Fax: (434)982-3139, e-mail: mitsu.okutsu@virginia.edu
Publications
1. Ogawa K, Suzuki K, Okutsu M, Yamazaki K, Shinkai S. The association of elevated reactive oxygen species level from neutrophils with low-grade inflammation in the elderly. Immun Ageing. 5:13-, 2008.
2. Okutsu M, Suzuki K, Ishijima T, Peake J, Higuchi M. The effects of acute exercise-induced cortisol on CCR2 expression on human monocytes. Brain, Behav, Immunity. 22(7):1066-71, 2008.
3. Okutsu M, Yoshida Y, Zhang X, Tamagawa A, Ohkubo T, Tsuji I, Nagatomi R. Exercise training enhances in vivo tuberculosis purified protein derivative response in the elderly. J Appl Physiol. 104(6):1690-6, 2008.
4. Peake J, Peiffer JJ, Abbiss CR, Nosaka K, Okutsu M, Laursen PB, Suzuki K. Body temperature and its effect on leukocyte mobilization, cytokines and markers of neutrophil activation during and after exercise. Eur J Appl Physiol. 102(4):391-401, 2008.
5. Shing CM, Peake JM, Suzuki K, Okutsu M, Pereira R, Stevenson L, Jenkins D, Coombes JS. Effects of Bovine Colostrum Supplementation on Immune Variables of Highly-Trained Cyclists. J Appl Physiol. 102(3):1113-22, 2007.
6. Suzuki K, Peake J, Nosaka K, Okutsu M, Abbiss CR, Surriano R, Bishop D, Quod MJ, Lee H, Martin DT, Laursen PB. Changes in markers of muscle damage, inflammation and HSP70 after an Ironman Triathlon race. Eur J Appl Physiol. 98(6):525-34, 2006.
7. Niu K, Hozawa A, Fujita K, Ohmori K, Okutsu M, Kuriyama S, Tsuji I, Nagatomi R. Influence of leisure-time physical activity on the relationship between C-reactive protein and hypertension in a community-based elderly population of Japan: the Tsurugaya project. Hypertens Res. 28(9):747-54, 2005.
8. Zhang X, Okutsu M, Kanemi O, Nagatomi R. Effect of foot shock stress on the interferon-gamma production of murine intestinal intraepithelial lymphocytes. Immunol Lett. 100(2):170-6, 2005.
9. Zhang X, Okutsu M, Kanemi O, Gametchu B, Nagatomi R. Repeated stress suppresses interferon-gamma production by murine intestinal intraepithelial lymphocytes. Tohoku J Exp Med. 206(3):203-12, 2005.
10. Okutsu M, Ishii K, Niu KJ, Nagatomi R. Cortisol-induced CXCR4 augmentation mobilizes T lymphocytes after acute physical stress. Am J Physiol Regul Integr Comp Physiol. 288(3)R591-1, 2005.

Review

1. Nagatomi R, Kaifu T, Okutsu M, Zhang X, Kanemi O, Ohmori H. Modulation of the immune system by the autonomic nervous system and its implication in immunological changes after training. Exerc Immunol Rev. 6:54-74, 2000.