Arginase: marker, effector, or candidate gene for asthma?
J. Clin. Invest. Donata Vercelli, et al. 111:1815 doi:10.1172/JCI18908 [
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Figure 1Arginine, arginase, and asthma. Arginase I and arginase II control the transformation of arginine into ornithine, which in turn gives rise to proline and polyamines. These products have multiple effects on connective tissue, smooth muscle, and mucus synthesis. Arginine also serves as a substrate for NO synthase (NOS), which generates NO, a critical regulator of airway physiology. The NOS and arginase pathways interfere with each other through substrate competition. Th2 cytokines induce arginase expression. During allergic inflammation, increased IL-4 and/or IL-13 expression results in increased expression of arginase and amplification of the arginase-dependent pathway, with concomitant suppression of NO generation. This leads to airway hyperresponsiveness and increased generation of mucus and collagen, all of which may contribute to the pathogenesis of asthma. The red arrows mark the upregulatory or downregulatory events that occur in arginine metabolism following increased expression of Th2 cytokines.
