Anti-inflammatory effect of arginase inhibitor and corticosteroid on airway allergic reactions in a Dermatophogoides farinae-induced NC/Nga mouse model.
The present study was aimed to investigate the effect of an arginase inhibitor, N-hydroxy-nor-L-arginine (nor-NOHA) and a corticosteroid, prednisolone, in an intranasal mite-induced NC/Nga mouse model of asthma. The treatment with nor-NOHA and prednisolone inhibited the increase in airway hyperresponsiveness, the number of bronchoalveolar lavage fluid cells, protein expression of arginase I and arginase II, messenger RNA (mRNA) expression of nitric oxide synthase (NOS)2 and Th2 cytokines such as interleukin (IL)-4, IL-5, and IL-13, and the pathological inflammatory changes of the lung. NOx levels in the lung were not changed in mice treated with prednisolone and elevated in mice treated with nor-NOHA or prednisolone plus nor-NOHA despite suppressed NOS2 mRNA expression. The study concluded that anti-inflammatory effect by nor-NOHA might be dependent on NO supply from depleted NO by downregulated arginine availability of arginase and was not related with the anti-inflammatory mechanisms by prednisolone.
Department of Public Health, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1, Shikata-cho, Okayama, 700-8558, Japan. kogino@md.okayama-u.ac.jp
Keiki
K
Ogino
Masayuki
M
Kubo
Hidekazu
H
Takahashi
Ran
R
Zhang
Yu
Y
Zou
Yoshihisa
Y
Fujikura
D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016084:Bronchoconstriction / Q000187:drug effects; D040001:Dermatophagoides farinae / Q000276:immunology; D004195:Disease Models, Animal; D018793:Interleukin-13 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D011239:Prednisolone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D018793:Interleukin-13; D015848:Interleukin-5; C404735:N(omega)-hydroxynorarginine; D012333:RNA, Messenger; D015847:Interleukin-4; D009569:Nitric Oxide; D001120:Arginine; D011239:Prednisolone; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C544448:Arg1 protein, mouse; C481673:Arg2 protein, mouse; D001119:Arginase