title: Toll-like receptor 4/nuclear factor-κB signaling pathway is involved in ACTG-toxin H-mediated anti-inflammatory effect.
abstract: ACTG-toxin H (AH) originates from Alternaria sp. In this study, we explored the molecular mechanism underlying the anti-inflammatory properties of AH. Treatment with AH inhibited lipopolysaccharide (LPS)-induced interleukin-6, IL-1β, inducible nitric oxide synthase, and cyclooxygenase-2 expression and nitric oxide production. Furthermore, AH inhibited LPS-induced P38 MAPK and Akt activation in RAW264.7 cells. Electrophoretic mobility shift assays (EMSAs) showed that AH inhibited LPS-induced nuclear factor-κB (NFκB) DNA-binding activity. Using transfection assay and measurement of an NFκB-sensitive promoter region, we found that transfection of toll-like receptor 4 (TLR4) increased LPS-induced NFκB transcription activity in 293T cells. AH significantly blocked LPS-induced NFκB activation in TLR4-transfected cells. Taken together, our data indicated that anti-inflammatory properties of AH resulted from the inhibition of proinflammatory cytokines and enzyme production via the TLR4/NFκB signaling pathway.
authors.affiliation: Department of Infection Biology, Zoonosis Research Center, Wonkwang University School of Medicine, Iksan, Jeonbuk, 570-749, South Korea.
authors.forename: Xinying
authors.initials: X
authors.lastname: Yang
authors.forename: Guojian
authors.initials: G
authors.lastname: Zhang
authors.forename: Xuelian
authors.initials: X
authors.lastname: Tang
authors.forename: Jieying
authors.initials: J
authors.lastname: Jiao
authors.forename: Sung Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Zhu
authors.forename: Dehai
authors.initials: D
authors.lastname: Li
authors.forename: Yong Gab
authors.initials: YG
authors.lastname: Yun
authors.forename: Qianqun
authors.initials: Q
authors.lastname: Gu
authors.forename: Hyun
authors.initials: H
authors.lastname: Park
mesh_terms: D000528:Alternaria / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D009183:Mycotoxins / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D004268:DNA-Binding Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009183:Mycotoxins; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases