Am J Clin Exp Immunol 2013;2(1):117-123

Original Article
Potent suppression of arginase 1 expression in murine macrophages by
low dose endotoxin

Michael J Surace, Liwu Li

Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061-0910

Received December 12, 2012; Accepted January 25, 2013; Epub February 27, 2013; Published March 9, 2013

Abstract: Macrophages can respond to diverse signals and adopt multiple phenotypes. Although interleukin-4 (IL-4) is
shown to potently induce the expression of arginase 1 and contribute to differentiation of macrophages to the
anti-inflammatory M2 phenotype, other modulators may potentiate or reduce the effect of IL-4. In this report, we focus on
the combinatorial effects of IL-4 with all-trans retinoic acid (ATRA) and lipopolysaccharide (LPS). ATRA has been shown
to contribute to the resolution of inflammation, however it has not been linked to arginase 1 expression in macrophages.
We demonstrate that although ATRA alone has no effect on the expression or activities of arginase 1, ATRA can
dramatically potentiate the induction of arginase 1 by IL-4. On the other hand, high doses of LPS, such as those seen in
septic shock, can induce the expression of both M1 and M2 mediators in macrophages. The effects of subclinical doses
of LPS, which are prevalent in humans with adverse health conditions, on macrophage differentiation are not well
studied. We demonstrate that low dose LPS can effectively suppress the expression of arginase 1 induced by IL-4 and
ATRA. Mechanistically, we report that the interleukin-1 receptor-associated kinase 1 (IRAK-1) and Toll-interacting-protein
(Tollip) are involved in the suppressive effect of low dose LPS. Our study reveals dynamic modulation of arginase 1
expression in macrophages by competing agonists, and bears relevance for potential intervention of chronic diseases.

Keywords: Low grade inflammation, molecular mechanisms, arginase expression, macrophages

Address correspondence to: Dr. Liwu Li, Life Science 1 Building, Washington Street, Department of Biology, Virginia
Tech, Blacksburg, VA 24061. Tel: 540-231-1433; Fax: 540-231-4043; E-mail:
AJCEI Copyright © 2012-present, All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711, USA