title: Protective effect of wogonin on proinflammatory cytokine generation via Jak1/3-STAT1/3 pathway in lipopolysaccharide stimulated BV2 microglial cells.
abstract: Wogonin is a flavonoid compound which exhibits antioxidation, anti-inflammation, neuroprotection, and antitumorgenesis functions. However, the mechanism of how wogonin reduces proinflammatory cytokine generation in activated microglia is unclear. At present, we found wogonin inhibited lipopolysaccharide (LPS)-/interferon-γ (INF-γ)-induced generation of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Wogonin exhibited parallel inhibition on LPS-/INF-γ-induced expression of IL-6 and TNF-α messenger RNA at the same concentration range. LPS-/INF-γ-induced phosphorylation of signal transduction and transcription 1 and 3 (STAT1/3) were also inhibited by wogonin. Although wogonin expressed only weak inhibitory effect on LPS-/INF-γ-induced phosphorylation of Janus kinase-2 (Jak-2) and tyrosine kinase (Tyk)-2, it significantly attenuated the phosphorylation of Jak-1 and Jak-3. These results indicated that the blockade of IL-6 and TNF-α production by wogonin in LPS-/INF-γ-stimulated BV2 microglial cells was attributed mainly to the interference in Jak-1/-3-STAT1/3 signaling pathway.
authors.affiliation: Department of Neurology, Show Chwan Memorial Hospital, Changhua, Taiwan.
authors.forename: Chung-Hsin
authors.initials: CH
authors.lastname: Yeh
authors.affiliation: Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taiwan Department of Pharmacy, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Hung-Che
authors.initials: HC
authors.lastname: Shih
authors.affiliation: School of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Hui-Mei
authors.initials: HM
authors.lastname: Hong
authors.affiliation: School of Public Health, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Shiuan-Shinn
authors.initials: SS
authors.lastname: Lee
authors.affiliation: Department of Anatomy, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Ming-Ling
authors.initials: ML
authors.lastname: Yang
authors.affiliation: Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan Center for General Education, Tunghai University, Taichung, Taiwan.
authors.forename: Chun-Jung
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taiwan Department of Pharmacy, Chung Shan Medical University Hospital, Taichung, Taiwan kuanyh@csmu.edu.tw.
authors.forename: Yu-Hsiang
authors.initials: YH
authors.lastname: Kuan
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000032:analysis / Q000378:metabolism*; D044950:Flavanones / Q000494:pharmacology*; D053612:Janus Kinases / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016207:Cytokines; D044950:Flavanones; D008070:Lipopolysaccharides; D050791:STAT Transcription Factors; D053612:Janus Kinases; C085514:wogonin
keywords: BV2 microglial cells; Jak; STAT; Wogonin; antiinflammation