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首页> 外文期刊>Journal of Cellular Physiology >G-protein coupled receptor kinase 5 mediates lipopolysaccharide-induced NFkappaB activation in primary macrophages and modulates inflammation in vivo in mice.
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G-protein coupled receptor kinase 5 mediates lipopolysaccharide-induced NFkappaB activation in primary macrophages and modulates inflammation in vivo in mice.

机译：g蛋白耦合受体激酶5介导lipopolysaccharide-induced NFkappaB激活主要的巨噬细胞和调节炎症在小鼠体内。

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摘要

G-protein coupled receptor kinase-5 (GRK5) is a serine/threonine kinase discovered for its role in the regulation of G-protein coupled receptor signaling. Recent studies have shown that GRK5 is also an important regulator of signaling pathways stimulated by non-GPCRs. This study was undertaken to determine the physiological role of GRK5 in Toll-like receptor-4-induced inflammatory signaling pathways in vivo and in vitro. Using mice genetically deficient in GRK5 (GRK5(-/-) ) we demonstrate here that GRK5 is an important positive regulator of lipopolysaccharide (LPS, a TLR4 agonist)-induced inflammatory cytokine and chemokine production in vivo. Consistent with this role, LPS-induced neutrophil infiltration in the lungs (assessed by myeloperoxidase activity) was markedly attenuated in the GRK5(-/-) mice compared to the GRK5(+/+) mice. Similar to the in vivo studies, primary macrophages from GRK5(-/-) mice showed attenuated cytokine production in response to LPS. Our results also identify TLR4-induced NFkappaB pathway in macrophages to be selectively regulated by GRK5. LPS-induced IkappaBalpha phosphorylation, NFkappaB p65 nuclear translocation, and NFkappaB binding were markedly attenuated in GRK5(-/-) macrophages. Together, our findings demonstrate that GRK5 is a positive regulator of TLR4-induced IkappaBalpha-NFkappaB pathway as well as a key modulator of LPS-induced inflammatory response.
机译：g蛋白耦合受体kinase-5 (GRK5)是一个丝氨酸/苏氨酸激酶发现的作用在g蛋白耦合受体的调节信号。也是一个信号通路的重要调节器由non-GPCRs刺激。进行确定的生理作用GRK5 toll样receptor-4-induced炎症信号通路在体内和体外。小鼠基因缺乏GRK5 (GRK5 (- / -))我们在这里展示GRK5是重要的积极监管机构的脂多糖(LPS全身的炎症细胞因子和TLR4受体激动剂)趋化因子生产体内。这个角色,LPS-induced嗜中性粒细胞浸润肺部(由髓过氧物酶活动评估)在GRK5明显减毒(- / -)小鼠相比GRK5(+ / +)老鼠。体内研究,主要从GRK5巨噬细胞(- / -)老鼠的细胞因子的生产对有限合伙人的回应。TLR4-induced NFkappaB通路在巨噬细胞被GRK5选择性地调节。IkappaBalpha磷酸化,NFkappaB p65核易位,NFkappaB绑定GRK5明显减(- / -)巨噬细胞。在一起,我们的研究结果表明,GRK5是a积极的监管机构TLR4-inducedIkappaBalpha-NFkappaB途径以及关键调制器的LPS-induced炎症反应。

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