LPS induces IL-10 production by human alveolar macrophages via MAPKinases- and Sp1-dependent mechanisms.
LPS induces IL-10 production by human alveolar macrophages via MAPKinases- and Sp1-dependent mechanisms.
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DOI：
10.1186/1465-9921-8-71
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发表时间：
2007-10-04
影响因子：
5.8
通讯作者：
Sibille Y
中科院分区：
文献类型：
--
作者：
Chanteux H;Guisset AC;Pilette C;Sibille Y
IL-10是主要由巨噬细胞产生的细胞因子，其在对吸入抗原的耐受性和肺内稳态中起关键作用。然而，其在肺泡巨噬细胞（HAM）（常驻肺吞噬细胞）中的调节仍然未知。本研究调查的作用，细胞内信号和转录因子控制的生产IL-10的LPS激活的HAM从正常的非吸烟志愿者。LPS（1-1000 pg/ml）诱导HAM在mRNA和蛋白水平上体外产生IL-10。LPS还激活ERK、p38和JNK MAP激酶的磷酸化（免疫印迹）和Sp-1核活性（EMSA）。MAP激酶的选择性抑制剂（分别为PD 98059、SB 203580和SP 600125）和Sp-1信号传导的选择性抑制剂（光神霉素）降低HAM中IL-10的表达。此外，虽然不影响IL-10 mRNA降解，但三种MAP激酶抑制剂完全消除了HAM中LPS对Sp-1的激活。这些结果第一次证明了LPS刺激的肺巨噬细胞中IL-10的表达依赖于ERK、p38和JNK MAP激酶的伴随激活，这些激酶控制着下游信号传导到Sp-1转录因子。该研究进一步指出Sp-1是肺中IL-10表达的关键信号传导途径。
IL-10 is a cytokine mainly produced by macrophages that plays key roles in tolerance to inhaled antigens and in lung homeostasis. Its regulation in alveolar macrophages (HAM), the resident lung phagocytes, remains however unknown. The present study investigated the role of intracellular signalling and transcription factors controlling the production of IL-10 in LPS-activated HAM from normal nonsmoking volunteers. LPS (1–1000 pg/ml) induced in vitro IL-10 production by HAM, both at mRNA and protein levels. LPS also activated the phosphorylation of ERK, p38 and JNK MAPkinases (immunoblots) and Sp-1 nuclear activity (EMSA). Selective inhibitors of MAPKinases (respectively PD98059, SB203580 and SP600125) and of Sp-1 signaling (mithramycin) decreased IL-10 expression in HAM. In addition, whilst not affecting IL-10 mRNA degradation, the three MAPKinase inhibitors completely abolished Sp-1 activation by LPS in HAM. These results demonstrate for the first time that expression of IL-10 in lung macrophages stimulated by LPS depends on the concomitant activation of ERK, p38 and JNK MAPKinases, which control downstream signalling to Sp-1 transcription factor. This study further points to Sp-1 as a key signalling pathway for IL-10 expression in the lung.
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DOI：
10.1016/s0162-3109(00)00199-5
发表时间：
2000-07-20
期刊：
IMMUNOPHARMACOLOGY
影响因子：
--
作者：
Jeon, YJ;Han, SH;Kim, HM
通讯作者：
Kim, HM
DOI：
10.1164/ajrccm.157.1.9703079
发表时间：
1998-01-01
影响因子：
24.7
作者：
John, M;Lim, S;Chung, KF
通讯作者：
Chung, KF
影响因子：
4.3
作者：
Koprak, S;Staruch, MJ;Dumont, FJ
通讯作者：
Dumont, FJ
影响因子：
4.4
作者：
Butcher, BA;Kim, L;Denkers, EY
通讯作者：
Denkers, EY
影响因子：
4.8
作者：
Bonello, MR;Khachigian, LM
通讯作者：
Khachigian, LM