title: Celastrol suppresses expression of adhesion molecules and chemokines by inhibiting JNK-STAT1/NF-κB activation in poly(I:C)-stimulated astrocytes.
abstract: In the central nervous system, viral infection can induce inflammation by up-regulating pro-inflammatory mediators that contribute to enhanced infiltration of immune cells into the central nervous areas. Celastrol is known to exert various regulatory functions, including anti-microbial activities. In this study, we investigated the regulatory effects and the mechanisms of action of celastrol against astrocytes activated with polyinosinic-polycytidylic acid (poly(I:C)), a synthetic dsRNA, as a model of pro-inflammatory mediated responses. Celastrol significantly inhibited poly(I:C)-induced expression of adhesion molecules, such as ICAM-1/VCAM-1, and chemokines, such as CCL2, CXCL8, and CXCL10, in CRT-MG human astroglioma cells. In addition, celastrol significantly suppressed poly(I:C)-induced activation of JNK MAPK and STAT1 signaling pathways. Furthermore, celastrol significantly suppressed poly(I:C)-induced activation of the NF-κB signaling pathway. These results suggest that celastrol may exert its regulatory activity by inhibiting poly(I:C)-induced expression of pro-inflammatory mediators by suppressing activation of JNK MAPK-STAT1/NF-κB in astrocytes. [BMB Reports 2017; 50(1): 25-30].
authors.affiliation: Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Korea.
authors.forename: Soo Yeon
authors.initials: SY
authors.lastname: An
authors.affiliation: Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Korea.
authors.forename: Gi Soo
authors.initials: GS
authors.lastname: Youn
authors.affiliation: Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Korea.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Korea.
authors.forename: Jinseu
authors.initials: J
authors.lastname: Park
mesh_terms: D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D018925:Chemokines / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D053978:Pentacyclic Triterpenes; D011070:Poly I-C / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
chemical_list: D018925:Chemokines; C573420:ICAM1 protein, human; D016328:NF-kappa B; D053978:Pentacyclic Triterpenes; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D014315:Triterpenes; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D048670:MAP Kinase Kinase 4; C050414:celastrol; D011070:Poly I-C