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p38δ在巨噬细胞中响应Toll样受体激活时控制丝裂原和应激激活激酶-1（MSK1）的功能。

p38δ controls Mitogen- and Stress-activated Kinase-1 (MSK1) function in response to toll-like receptor activation in macrophages.

机构信息

Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC (CNB-CSIC), Madrid, Spain.

Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología/CSIC (CNB-CSIC), Madrid, Spain.

出版信息

Front Cell Dev Biol. 2023 Feb 9;11:1083033. doi: 10.3389/fcell.2023.1083033. eCollection 2023.

DOI:10.3389/fcell.2023.1083033
PMID:36846591
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9946961/
Abstract

Mitogen- and Stress-activated Kinase (MSK) 1 is a nuclear protein, activated by p38α Mitogen-Activated Kinase (MAPK) and extracellular signal-regulated kinase (ERK1/2), that modulate the production of certain cytokines in macrophages. Using knockout cells and specific kinase inhibitors, we show that, besides p38α and ERK1/2, another p38MAPK, p38δ, mediates MSK phosphorylation and activation, in LPS-stimulated macrophages. Additionally, recombinant MSK1 was phosphorylated and activated by recombinant p38δ, to the same extent than by p38α, in experiments. Moreover, the phosphorylation of the transcription factors CREB and ATF1, that are MSK physiological substrates, and the expression of the CREB-dependent gene encoding DUSP1, were impaired in p38δ-deficient macrophages. Also, the transcription of IL-1Ra mRNA, that is MSK-dependent, was reduced. Our results indicate that MSK activation can be one possible mechanism by which p38δ regulates the production of a variety of inflammatory molecules involved in immune innate response.

摘要

丝裂原和应激激活激酶（MSK）1是一种核蛋白，可被p38α丝裂原活化蛋白激酶（MAPK）和细胞外信号调节激酶（ERK1/2）激活，它能调节巨噬细胞中某些细胞因子的产生。利用基因敲除细胞和特异性激酶抑制剂，我们发现，在脂多糖刺激的巨噬细胞中，除了p38α和ERK1/2外，另一种p38丝裂原活化蛋白激酶p38δ也介导MSK的磷酸化和激活。此外，在实验中，重组MSK1被重组p38δ磷酸化并激活，其程度与被p38α激活的程度相同。而且，在p38δ缺陷的巨噬细胞中，MSK的生理底物——转录因子CREB和ATF1的磷酸化以及编码双特异性磷酸酶1（DUSP1）的CREB依赖性基因的表达均受到损害。此外，依赖于MSK的白细胞介素-1受体拮抗剂（IL-1Ra）mRNA的转录也减少。我们的结果表明，MSK激活可能是p38δ调节参与先天性免疫反应的多种炎症分子产生的一种机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffce/9946961/1a5a7fdb4841/fcell-11-1083033-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffce/9946961/057f9564c0c5/fcell-11-1083033-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffce/9946961/1a5a7fdb4841/fcell-11-1083033-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffce/9946961/057f9564c0c5/fcell-11-1083033-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffce/9946961/f31451fff159/fcell-11-1083033-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffce/9946961/e36416115582/fcell-11-1083033-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffce/9946961/72f4c7588ee7/fcell-11-1083033-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffce/9946961/1a5a7fdb4841/fcell-11-1083033-g005.jpg

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