Cross-talk between CD38 and TTP Is Essential for Resolution of Inflammation during Microbial Sepsis
Cross-talk between CD38 and TTP Is Essential for Resolution of Inflammation during Microbial Sepsis
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DOI：
10.1016/j.celrep.2019.12.090
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发表时间：
2020-01-28
期刊：
影响因子：
8.8
通讯作者：
Chung, Hun Taeg
中科院分区：
文献类型：
--
作者：
Joe, Yeonsoo;Chen, Yingqing;Chung, Hun Taeg
急性炎症的消退阶段对于组织稳态是必不可少的，但其潜在机制仍不清楚。我们证明，炎症的解决涉及CD38和tristetraprolin（TTP）之间的相互作用。在急性炎症发作期间，CD38水平升高，导致从NAD（P）（+）产生Ca2+信号传导信使、烟酸腺嘌呤二核苷酸磷酸（NAADP）、ADP核糖（ADPR）和环ADPR（cADPR）。为了开始消退，TTP表达通过第二信使NAADP和cADPR增加，其下调CD38表达。Sirt1依赖性去乙酰化激活TTP，响应NAD（+）水平升高，抑制急性炎症反应，降低Rheb表达，抑制mTORC 1，并诱导自体吞噬溶酶体清除细菌。TTP可能代表抗炎剂（如一氧化碳）的机制靶点。TTP介导急性炎症和细菌自噬清除受损组织在脓毒症期间炎症消退中的串扰。
The resolution phase of acute inflammation is essential for tissue homeostasis, yet the underlying mechanisms remain unclear. We demonstrate that resolution of inflammation involves interactions between CD38 and tristetraprolin (TTP). During the onset of acute inflammation, CD38 levels are increased, leading to the production of Ca2+- signaling messengers, nicotinic acid adenine dinucleotide phosphate (NAADP), ADP ribose (ADPR), and cyclic ADPR (cADPR) from NAD(P)(+). To initiate the onset of resolution, TTP expression is increased by the second messengers, NAADP and cADPR, which downregulate CD38 expression. The activation of TTP by Sirt1-dependent deacetylation, in response to increased NAD(+) levels, suppresses the acute inflammatory response and decreases Rheb expression, inhibits mTORC1, and induces auto-phagolysosomes for bacterial clearance. TTP may represent a mechanistic target of anti-inflammatory agents, such as carbon monoxide. TTP mediates crosstalk between acute inflammation and autophagic clearance of bacteria from damaged tissue in the resolution of inflammation during sepsis.