NOS1号
巨噬细胞极化
AP-1转录因子
促炎细胞因子
细胞生物学
信号转导
IRF5公司
TLR4型
一氧化氮合酶
转录因子
生物
表型
炎症
化学
一氧化氮
免疫学
干扰素调节因子
生物化学
内分泌学
基因
作者
Mansi Srivastava,Uzma Saqib,Adnan Naim,Anjali Roy,Dongfang Liu,Deepak Bhatnagar,Ravinder Ravinder,Mirza S. Baig
标识
DOI:10.1007/s00011-016-1017-z
摘要
Macrophages polarize to proinflammatory M1 or anti-inflammatory M2 states with distinct physiological functions. This transition within the M1–M2 phenotypes decides the nature, duration and severity of an inflammatory response. Although there is a substantial understanding of the fate of these phenotypes, the underlying molecular mechanism of transition within the M1–M2 phenotypes is not well understood. We have investigated the role of neuronal nitric oxide synthase (NOS1)-mediated regulation of activator protein 1 (AP-1) transcription factor in macrophages as a critical effector of macrophage phenotypic change. Raw 264.7 and THP1 macrophages were stimulated with LPS (250 ng/ml) to activate the inflammatory signaling pathway. We analyzed the effect of pharmacological NOS1 inhibitor: TRIM (1-(2- Trifluoromethylphenyl) imidazole) on LPS-induced inflammatory response in macrophages. We determined that NOS1-derived nitric oxide (NO) facilitate Fos and Jun interaction which induces IL-12 & IL-23 expression. Pharmacological inhibition of NOS1 inhibits ATF2 and Jun dimer. Switching of Fos and Jun dimer to ATF2 and Jun dimerization controls phenotype transition from IL-12high IL-23high IL-10low to IL-12low IL-23lowIL-10high phenotype, respectively. These findings highlight a key role of the TLR4-NOS1-AP1 signaling axis in regulating macrophage polarization.
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