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Am J Physiol Regul Integr Comp Physiol 276: R237-R242, 1999;
0363-6119/99 $5.00
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Vol. 276, Issue 1, R237-R242, January 1999

Regulation of arginase isoforms I and II by IL-4 in cultured murine peritoneal macrophages

Claudine A. Louis, Vino Mody, William L. Henry Jr., Jonathan S. Reichner, and Jorge E. Albina

Department of Surgery, Division of Surgical Research, Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island 02903

Macrophages can express two arginase isoforms with distinct subcellular localization (cytosolic AI and mitochondrial AII). These isoforms are products of different genes and are capable of differential induction. Experiments were performed to identify the specific arginase isoforms induced by interleukin (IL)-4, a Th2 cytokine shown by others to increase arginase activity in macrophages, and serum. Results indicate IL-4, in concert with serum, increases AI, but not AII, mRNA in cultured murine macrophages. Moreover, they show serum to induce both arginase isoforms and to be required for maximal AI induction by IL-4. Together with the enhanced expression of AI, IL-4 induced the expression of the cationic amino acid transporter MCAT-2 and increased L-arginine transport into the cells. Present results confirm, then, specificity in the ability of macrophage arginase isoforms to be induced by different stimuli. Moreover, they suggest that a decrease in intracellular L-arginine concentration resulting from its consumption by arginase may be repaired by concurrent increases in L-arginine influx into the cell.

L-arginine; cytokines; amino acid transport; interleukin-4


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