Contrasting effects of proinflammatory and T-helper lymphocyte subset-2 cytokines on the 5-lipoxygenase pathway in monocytes.
Contrasting effects of proinflammatory and T-helper lymphocyte subset-2 cytokines on the 5-lipoxygenase pathway in monocytes.
复制标题
促炎细胞因子和 T 辅助淋巴细胞亚群 2 细胞因子对单核细胞 5-脂氧合酶途径的影响对比。
DOI：
10.1038/ki.1997.209
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发表时间：
1997
影响因子：
19.6
通讯作者：
Badr,KF
中科院分区：
文献类型：
--
作者：
Nassar,GM;Montero,A;Fukunaga,M;Badr,KF
Contrasting effects of proinflammatory and T-helper lymphocyte subset-2 cytokines on the 5-lipoxygenase pathway in monocytes.Human peripheral blood monocytes (HPBMs) express 5-lipoxygenase (5-LO) and 5-LO activating protein (FLAP), and hence have an ability to synthesize proinflammatory leukotrienes (LTs). Regulation of 5-LO and FLAP expression is a major determinant of cellular LT synthesis. We examined the effects of proinflammatory [interleukin (IL)-1 and interferon (IFN)-γ] and T helper lymphocyte subset 2 (TH-2; IL-4 and IL-13) cytokines on (1) LTB4 production, and (2) 5-LO and FLAP expression in HPBMs. We show that IL-1 and IFN-γstimulate, whereas IL-4 and IL-13 inhibit ionophore-activated LTB4 release. The stimulatory effects of IL-1 and IFN-ywere apparent at 16 to 36 hours of incubation. IL-1 modestly increased FLAP mRNA and significantly increased 5-LO mRNA steady state levels at 24 and 36 hours of incubation, respectively. IFN-γdid not change the mRNA or protein expression of either 5-LO or FLAP. The inhibitory effects of IL-4 and IL-13 were associated with decreased FLAP mRNA and protein steady state levels. These results demonstrate that regulation of monocyte LTB4 biosynthesis by different cytokines proceeds via different pathways that partly involve modulation of the expression of the key proteins, 5-LO and FLAP. In addition, the contrasting effects of proinflammatory and TH-2-derived cytokines on moncyte LTB4 production demonstrate mechanisms by which cytokine subpopulations may modulate monocyte function in inflammation.
