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Quantitative proteomic analysis reveals that lipopolysaccharide induces mitogen‐activated protein kinase‐dependent activation in human microglial cells
Author(s) -
Byun Kyunghee,
Young Kim Jin,
Bayarsaikhan Enkhjargal,
Kim Daesik,
Jeong GooBo,
Yun Ki Na,
Kyeong Min Hye,
Kim Seung U.,
Yoo Jong Shin,
Lee Bonghee
Publication year - 2012
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.201200345
Subject(s) - microglia , microbiology and biotechnology , mapk/erk pathway , p38 mitogen activated protein kinases , tumor necrosis factor alpha , chemokine , protein kinase a , biology , kinase , lipopolysaccharide , signal transduction , downregulation and upregulation , inflammation , chemistry , immunology , biochemistry , gene
Microglial cells act as the first and main form of active immune defense in the central nervous system related to inflammation and neurodegenerative disease. Lipopolysaccharide ( LPS ) induces many genes encoding inflammatory mediators, including cytokines such as tumor necrosis factor‐α, interleukin‐1β, ( IL ‐1β), and IL ‐6, chemokines, and prostaglandins in microglial cells. Quantitative proteomics methods with isobaric chemical labeling using tandem mass tags and 2 D ‐nano LC ‐ ESI ‐ MS / MS were used to systematically analyze proteomic changes in microglia responding to LPS stimulation. As a result, we found that the expression level of 21 proteins in human microglial cells changed after activation. Among those, one of the strong mitogen‐activated protein kinase ( MAPK ) regulator proteins, CMPK 1 was highly upregulated after LPS stimulation in human microglial cells. We detected and validated upregulation of MAPK including ERK 1/2, p38, and SAPK / JNK by immunohistochemistry and W estern blotting. NF κ B , strong transcription factor of CMPK 1, was translocated to the nucleus from the cytosol by high contents screening after LPS stimulation. Taken together, we conclude that MAPK signaling plays an important role in LPS ‐induced human microglial activation related to inflammatory response.