title: Quantitative proteomic analysis reveals that lipopolysaccharide induces mitogen-activated protein kinase-dependent activation in human microglial cells.
abstract: 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 2D-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, CMPK1 was highly upregulated after LPS stimulation in human microglial cells. We detected and validated upregulation of MAPK including ERK1/2, p38, and SAPK/JNK by immunohistochemistry and Western blotting. NFκB, strong transcription factor of CMPK1, 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.
authors.affiliation: Center for Genomics and Proteomics, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Korea.
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Byun
authors.forename: Jin
authors.initials: J
authors.lastname: Young Kim
authors.forename: Enkhjargal
authors.initials: E
authors.lastname: Bayarsaikhan
authors.forename: Daesik
authors.initials: D
authors.lastname: Kim
authors.forename: Goo-Bo
authors.initials: GB
authors.lastname: Jeong
authors.forename: Ki Na
authors.initials: KN
authors.lastname: Yun
authors.forename: Hye
authors.initials: H
authors.lastname: Kyeong Min
authors.forename: Seung U
authors.initials: SU
authors.lastname: Kim
authors.forename: Jong Shin
authors.initials: JS
authors.lastname: Yoo
authors.forename: Bonghee
authors.initials: B
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D015180:Electrophoresis, Gel, Two-Dimensional; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D020543:Proteome / Q000187:drug effects*; D040901:Proteomics / Q000379:methods; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D020543:Proteome; D020928:Mitogen-Activated Protein Kinases