Lee Sang-Min, Suk Kyoungho, Lee Won-Ha
School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Republic of Korea.
Department of Pharmacology, Brain Science & Engineering Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
Cell Immunol. 2015 Aug;296(2):115-21. doi: 10.1016/j.cellimm.2015.04.004. Epub 2015 Apr 24.
MARCKS, a substrate of protein kinase C, is involved in various processes associated with cytoskeletal movement. Although the expression of MARCKS is highly induced in macrophages, its role in macrophage function has not been studied in detail. Notably, the suppression of MARCKS expression in macrophage cell lines blocked LPS-induced expression of TNF-α at the transcriptional level. Treatment of macrophages with MARCKS N-terminus sequence (MANS) and effector domain (ED) peptides, which mimic functional domains and block the phosphorylation of MARCKS, suppressed the LPS-induced expression of TNF-α through suppression of p38 and JNK MAPKs and NF-κB. Treatment of mice with MANS peptide reduced serum TNF-α and IL-6 levels and resulted in 40% survival of mice after the administration of a lethal dose of LPS. These data demonstrate that MARCKS is involved in the regulation of proinflammatory cytokine expression in macrophages and that MARCKS-derived peptides can be used to suppress inflammatory responses.
MARCKS是蛋白激酶C的一种底物，参与与细胞骨架运动相关的各种过程。尽管MARCKS在巨噬细胞中的表达被高度诱导，但其在巨噬细胞功能中的作用尚未得到详细研究。值得注意的是，巨噬细胞系中MARCKS表达的抑制在转录水平上阻断了LPS诱导的TNF-α表达。用模拟功能域并阻断MARCKS磷酸化的MARCKS N端序列（MANS）和效应器结构域（ED）肽处理巨噬细胞，通过抑制p38和JNK MAPKs以及NF-κB，抑制了LPS诱导的TNF-α表达。用MANS肽处理小鼠可降低血清TNF-α和IL-6水平，并使给予致死剂量LPS后40%的小鼠存活。这些数据表明，MARCKS参与巨噬细胞中促炎细胞因子表达的调节，并且MARCKS衍生肽可用于抑制炎症反应。
