半胱氨酰白三烯在人单核细胞/巨噬细胞中诱导巨噬细胞炎性蛋白-1。
Cysteinyl leukotrienes induce macrophage inflammatory protein-1 in human monocytes/macrophages.
作者信息
Ichiyama Takashi, Hasegawa Masanari, Hashimoto Kunio, Matsushige Takeshi, Hirano Reiji, Furukawa Susumu
机构信息
Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
出版信息
Int Arch Allergy Immunol. 2009;148(2):147-53. doi: 10.1159/000155745. Epub 2008 Sep 19.
BACKGROUND
Macrophage inflammatory protein-1alpha (MIP-1alpha) and MIP-1beta are known for their chemotactic and proinflammatory effects on monocytes/macrophages which have a cysteinyl leukotriene 1 (CysLT(1)) receptor.
METHODS
We examined MIP-1alpha and MIP-1beta production stimulated by CysLTs (LTC(4), LTD(4), and LTE(4)) in THP-1 cells, a human monocytic leukemia cell line, and peripheral blood mononuclear cells (PBMCs). Moreover, we examined the inhibitory effect of pranlukast, a CysLT(1) receptor antagonist, and inhibitors of three major mitogen-activated protein kinases (MAPK) on the induction of MIP-1alpha and MIP-1beta production by CysLTs.
RESULTS
ELISA demonstrated that CysLTs induced MIP-1alpha and MIP-1beta production in THP-1 cells and PBMCs. PCR demonstrated that LTD(4) increased MIP-1alpha and MIP-1beta mRNA expressions in THP-1 cells. Pranlukast blocked MIP-1alpha and MIP-1beta production promoted by LTD(4) in THP-1 cells and PBMCs. Moreover, an inhibitor of extracellular signal-regulated kinase (ERK) attenuated the induction of MIP-1alpha and MIP-1beta production by LTD(4) in THP-1 cells whereas the inhibitors of c-Jun NH2-terminal kinase or p38 MAPK did not.
CONCLUSION
CysLTs induce MIP-1alpha and MIP-1beta production mediated by ERK via binding to the CysLT(1) receptor in human monocytes/macrophages.
背景
巨噬细胞炎性蛋白-1α（MIP-1α）和MIP-1β因其对具有半胱氨酰白三烯1（CysLT(1)）受体的单核细胞/巨噬细胞的趋化和促炎作用而闻名。
方法
我们检测了半胱氨酰白三烯（LTC(4)、LTD(4)和LTE(4)）刺激人单核细胞白血病细胞系THP-1细胞和外周血单个核细胞（PBMCs）产生MIP-1α和MIP-1β的情况。此外，我们检测了半胱氨酰白三烯1（CysLT(1)）受体拮抗剂普仑司特以及三种主要的丝裂原活化蛋白激酶（MAPK）抑制剂对由半胱氨酰白三烯诱导的MIP-1α和MIP-1β产生的抑制作用。
结果
酶联免疫吸附测定（ELISA）表明，半胱氨酰白三烯可诱导THP-1细胞和PBMCs产生MIP-1α和MIP-1β。聚合酶链反应（PCR）表明，LTD(4)可增加THP-1细胞中MIP-1α和MIP-1β的信使核糖核酸（mRNA）表达。普仑司特可阻断LTD(4)在THP-1细胞和PBMCs中促进的MIP-1α和MIP-1β的产生。此外，细胞外信号调节激酶（ERK）抑制剂可减弱LTD(4)在THP-1细胞中诱导的MIP-1α和MIP-1β的产生，而c-Jun氨基末端激酶或p38丝裂原活化蛋白激酶（p38 MAPK）抑制剂则无此作用。
结论
在人单核细胞/巨噬细胞中，半胱氨酰白三烯通过与CysLT(1)受体结合，经ERK介导诱导MIP-1α和MIP-1β的产生。
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