Th2 response of human peripheral monocytes involves isoform-specific induction of monoamine oxidase-A.
Monocyte/macrophage function is critically regulated by specific cytokines and growth factors that they are exposed to at inflammatory sites. IL-4 and IL-13 are multifunctional cytokines generated mainly by Th2 lymphocytes that have important biological activities in allergy and inflammation. The Th2 response of human peripheral monocytes is characterized by complex alterations in the gene expression pattern, which involves dominant expression of CD23 cell surface Ag and lipid-peroxidizing 15-lipoxygenase-1 (15-LOX1). In this study, we report that the classical Th2 cytokines IL-4 and IL-13 strongly up-regulate expression of monoamine oxidase A (MAO-A) with no induction of the closely related isozyme, MAO-B. Real-time PCR indicated a >2000-fold up-regulation of the MAO-A transcripts, and immunohistochemistry revealed coexpression of the enzyme with 15-LOX1 in a major subpopulation of monocytes. MAO-A was also induced in lung carcinoma A549 cells by IL-4 in parallel with 15-LOX1. In promyelomonocytic U937 cells, which neither express 15-LOX1 nor MAO-A in response to IL-4 stimulation, expression of MAO-A was up-regulated following transfection with 15-LOX1. This is the first report indicating expression of MAO-A in human monocytes. Its isoform-specific up-regulation in response to Th2 cytokines suggests involvement of the enzyme in modulation of innate and/or acquired immune system.
Institute of Biochemistry, University Clinics Charité, Humboldt University, Berlin, Germany.
Pavlos
P
Chaitidis
Ellen E
EE
Billett
Valerie B
VB
O'Donnell
Alexandra Bermudez
AB
Fajardo
Julia
J
Fitzgerald
Ralf J
RJ
Kuban
Ute
U
Ungethuem
Hartmut
H
Kühn
D001093:Arachidonate 15-Lipoxygenase / Q000502:physiology; D004790:Enzyme Induction; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis*; D008995:Monoamine Oxidase / Q000096:biosynthesis* / Q000235:genetics; D009000:Monocytes / Q000201:enzymology / Q000502:physiology*; D018418:Th2 Cells / Q000276:immunology*
D018793:Interleukin-13; D007527:Isoenzymes; D015847:Interleukin-4; D001093:Arachidonate 15-Lipoxygenase; D008995:Monoamine Oxidase