Toll-like receptor 4/nuclear factor-κB signaling pathway is involved in ACTG-toxin H-mediated anti-inflammatory effect

• Published in: Molecular and cellular biochemistry 2013-02, Vol.374 (1-2), p.29-36
• Main Authors: Yang, Xinying, Zhang, Guojian, Tang, Xuelian, Jiao, Jieying, Kim, Sung Yeon, Lee, Joo Young, Zhu, Tianjiao, Li, Dehai, Yun, Yong Gab, Gu, Qianqun, Park, Hyun
• Format: Article
• Language: English
• Subjects: AKT protein; Alternaria; Alternaria - metabolism; Animals; Anti-Inflammatory Agents - pharmacology; Biochemistry; Biomedical and Life Sciences; Cardiology; Cell Line; Cell Survival; COX-2 inhibitors; Cyclooxygenase 2 - metabolism; DNA; DNA-Binding Proteins - metabolism; Enzyme Activation - drug effects; Enzymes; Genetic research; HEK293 Cells; Humans; Infection; Inflammation - immunology; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; Life Sciences; Lipopolysaccharides; Macrophages - metabolism; Medical Biochemistry; Mice; Mitogens; Mycotoxins - pharmacology; NF-kappa B - metabolism; Nitric oxide; Nitric Oxide - biosynthesis; Nitric Oxide Synthase Type II - metabolism; Oncology; p38 Mitogen-Activated Protein Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction; T cells; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-012-1502-9

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.