title: Cytokine modulation of LDL oxidation by activated human monocytes.
abstract: There is considerable evidence to suggest that cytokines modulate the pathological cellular events that occur in human atherosclerosis. We sought to determine the effects of T-helper-lymphocyte (TH)-1- and TH2-type cytokines on the ability of human monocytes to oxidize LDL, one of the pathological processes believed to occur in atherosclerosis. The ability of opsonized zymosan (ZOP)-activated human monocytes to oxidize LDL in a 24-hour period was significantly enhanced by pretreatment of the monocytes with the TH2 cytokines, interleukin (IL)-4, or IL-13 compared with untreated monocytes. In contrast, interferon (IFN)-gamma, a TH1 cytokine, inhibited LDL oxidation by activated monocytes. Treatment with IFN-gamma also prevented the IL-4- and IL-13-mediated enhancement of LDL oxidation by ZOP-activated monocytes. Untreated or cytokine-treated unactivated monocytes did not oxidize LDL. The enhancement of LDL oxidation mediated by IL-4 or IL-13 treatment was not due to a mitogenic effect of the cytokines on the monocytes, nor to modulation of superoxide anion (O2-) production. The cytokine regulation of 15-lipoxygenase (LO) in the monocytes was also examined. IL-4 and IL-13 induction of 15-LO mRNA and 15-LO activity in the monocytes was confirmed, as was the previously reported inhibition of induction by IFN-gamma. In summary, IL-4 and IL-13 enhance the ability of activated human monocytes to oxidize LDL, whereas IFN-gamma inhibits the cell-mediated oxidation. The up- and downregulation of activated monocyte-mediated LDL oxidation by these cytokines correlates with the expression of 15-LO activity. Considerable evidence suggests that the progression of atherosclerosis includes events that are immunologically mediated, lending potential physiological relevance to these in vitro observations.
authors.affiliation: Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, OH 44195 USA.
authors.forename: V A
authors.initials: VA
authors.lastname: Folcik
authors.forename: R
authors.initials: R
authors.lastname: Aamir
authors.forename: M K
authors.initials: MK
authors.lastname: Cathcart
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D010084:Oxidation-Reduction; D013481:Superoxides / Q000378:metabolism
chemical_list: D016207:Cytokines; D018793:Interleukin-13; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D013481:Superoxides; D015847:Interleukin-4; D007371:Interferon-gamma