Reciprocal regulation of LTA(4) hydrolase expression in human monocytes by gamma-interferon and interleukins 4 and 13: potential relevance to leukotriene regulation in glomerular disease.
Reciprocal regulation of LTA(4) hydrolase expression in human monocytes by gamma-interferon and interleukins 4 and 13: potential relevance to leukotriene regulation in glomerular disease.
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γ-干扰素和白细胞介素 4 和 13 对人单核细胞中 LTA(4) 水解酶表达的相互调节：与肾小球疾病中白三烯调节的潜在相关性。
DOI：
10.1159/000020677
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Badr,KF
中科院分区：
文献类型：
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作者：
Montero,A;Nassar,GM;Uda,S;Munger,KA;Badr,KF
白三烯4a （lta4）水解酶催化合成白三烯b4 （lta4）的最后一步。th -1和th -2来源的细胞因子可能通过影响lta4水解酶的表达来调节单核细胞合成lta4。方法将新鲜分离的单核细胞与促炎因子和抗炎因子孵育36 h，采用Northern blot法检测mRNA表达，Western blot法检测蛋白表达，ELISA法检测ltb4合成。结果干扰素-γ （th -2来源的细胞因子）显著增加lta4水解酶mRNA的表达，而白细胞介素(IL)-4和IL-13 （th -2来源的细胞因子）降低lta4水解酶mRNA的表达。与th -1或th -2来源的细胞因子孵育单核细胞后，免疫反应性lta4水解酶的表达也有相同的影响。单核细胞源性细胞因子IL-1β对lta4水解酶mRNA表达无显著影响。测量LTB -4释放量时，IL-1β和干扰素-γ均能显著增加单核细胞产生LTB -4，而TH-2细胞因子（IL-4和IL-13）则能降低LTB -4的产生。结论th -1和th -2来源的细胞因子对lta4水解酶mRNA表达的相反作用可能调节炎症过程中单核细胞对lta4的合成。
Background/AimsLeukotriene A 4 (LTA 4) hydrolase catalyzes the final step in the synthesis of leukotriene B 4 (LTB 4). TH-1-and TH-2-derived cytokines may regulate LTB 4 synthesis by monocytes through their actions on the expression of LTA 4 hydrolase.MethodsFreshly isolated monocytes were incubated with pro-and anti-inflammatory cytokines for 36 h. mRNA expression was determined by Northern blot, protein expression was determined by Western blot and LTB 4 synthesis was determined by ELISA.ResultsInterferon-γ (a TH-2-derived cytokine) increased significantly LTA 4 hydrolase mRNA expression, whereas interleukin (IL)-4 and IL-13 (both TH-2-derived cytokines) decreased LTA 4 hydrolase mRNA expression in these cells. The same effects were seen on the expression of immunoreactive LTA 4 hydrolase after incubating the monocytes with either TH-1-or TH-2-derived cytokines. The monocyte-derived cytokine IL-1β did not show any significant effect on LTA 4 hydrolase mRNA expression. When LTB 4 release was measured, both IL-1β and interferon-γ significantly increased LTB 4 production by monocytes, while TH-2 cytokines (IL-4 and IL-13) decreased it.ConclusionThe opposing effects of TH-1-and TH-2-derived cytokines on the expression of LTA 4 hydrolase mRNA may regulate LTB 4 synthesis by monocytes during inflammation.