Reciprocal regulation of LTA(4) hydrolase expression in human monocytes bygamma-interferon and interleukins 4 and 13: Potential relevance to leukotriene regulation in glomerular disease

Background/Aims:Leukotriene A(4) (LTA(4)) hydrolase catalyzes the final ste p in the synthesis of leukotriene B-4 (LTB4). TH-1- and TH-2-derived cytoki nes may regulate LTB4 synthesis by monocytes through their actions on the e xpression of LTA(4) hydrolase. Methods: Freshly isolated monocytes were inc ubated with pro- and antiinflammatory cytokines for 36 h. mRNA expression w as determined by Northern blot, protein expression was determined by Wester n blot and LTB4 synthesis was determined by ELISA. Results: Interferon-gamm a (a TH-2-derived cytokine) increased significantly LTA(4) hydrolase mRNA e xpression, whereas interleukin (IL)-4 and IL-13 (both TH-2-derived cytokine s) decreased LTA(4) hydrolase mRNA expression in these cells. The same effe cts were seen on the expression of immunoreactive LTA(4) hydrolase after in cubating the monocytes with either TH-1- or TH-2-derived cytokines. The mon ocyte-derived cytokine IL-1 beta did not show any significant effect on LTA (4) hydrolase mRNA expression. When LTB4 release was measured, both IL-1 be ta and interferon-gamma significantly increased LTB4 production by monocyte s, while TH-2 cytokines (IL-4 and IL-13) decreased it. Conclusion: The oppo sing effects of TH-1- and TH-2-derived cytokines on the expression of LTA(4 ) hydrolase mRNA may regulate LTB4 synthesis by monocytes during inflammati on. Copyright (C) 1999 S. Karger AG, Basel.