Induction of 15-lipoxygenase by interleukin-13 in human blood monocytes.
15-Lipoxygenase (15-LO) catalyzes hydroperoxidation of fatty acids, a reaction of potential relevance to inflammation, membrane remodeling, and atherosclerosis. In human leukocytes, 15-lipoxygenation of arachidonic acid produces 15-(S)-hydroxyeicosatetraenoic acid and lipoxin A4, which suppress white cell chemotaxis, adherence, and activation, and antagonize proinflammatory leukotrienes. Interleukin (IL)-13, produced by T-helper subset 2 (TH-2) lymphocytes, specifically and potently induced 15-LO gene expression and enzyme activity in human monocytes. Among other TH-2 lymphokines, this induction of 15-LO is shared by IL-4 but not by IL-10. Interferon-gamma, a product of TH-1 lymphocytes, blocked IL-13-mediated induction of 15-LO. The induction of the anti-inflammatory 15-LO pathway by IL-13 reveals a new facet of IL-13 biology that supports its role as a cytokine with potential to down-regulate inflammatory pathways. The contrasting effects of interferon-gamma and IL-13 on 15-LO induction demonstrate mechanisms by which T-lymphocyte subsets may modulate macrophage/monocyte function in inflammation or atherosclerosis.
Nassar
G M
GM
Department of Medicine, Emory University, Atlanta, Georgia.
Morrow
J D
JD
Roberts
L J
LJ
Lakkis
F G
FG
Badr
K F
KF
D001093:Arachidonate 15-Lipoxygenase / Q000096:biosynthesis*; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000201:enzymology*; D012333:RNA, Messenger / Q000235:genetics
D017931:DNA Primers; D006893:Hydroxyeicosatetraenoic Acids; D018793:Interleukin-13; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D001093:Arachidonate 15-Lipoxygenase