Differential sensitivities of human blood monocytes and alveolar macrophages to the inhibition of prostaglandin endoperoxide synthase-2 by interleukin-4.
Interleukin-4 (IL-4) is a potent immunomodulatory cytokine synthesized and released by Th2 lymphocytes, mast cells and basophils. It has important effects on monocyte/macrophage cell lines, regulating the secretion of several cytokines, and the production of eicosanoids. In human monocytes and macrophages, IL-4 increases the expression of 15-lipoxygenase and 15-HETE production, but suppresses the inducible isoform of the prostaglandin H synthase (PGHS-2) enzyme and prostanoid synthesis. Prostanoids, in particular prostaglandin E2 (PGE2) have important functions in modulating inflammatory and fibrotic processes. We compared the effect of IL-4 on the expression of PGHS-2 in human alveolar macrophages (AM) and blood monocytes (BM) activated with physiologically distinct stimuli, lipopolysaccharide (LPS) or IL-1 in vitro. The induction of PGHS-2 mRNA and protein, and prostanoid synthesis by all stimuli was inhibited by exogenous IL-4 in both cell types. However, monocytes were more susceptible to this effect of IL-4 than alveolar macrophages.
Dworski
R
R
Center for Lung Research, Vanderbilt University School of Medicine, Nashville, TN 37232-2650, USA.
Sheller
J R
JR
D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D011453:Prostaglandins / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D012333:RNA, Messenger; D015847:Interleukin-4; D011451:Prostaglandin-Endoperoxide Synthases