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Pipoxolan suppresses the inflammatory factors of NF‐κB , AP ‐1, and STATs , but activates the antioxidative factor Nrf2 in LPS ‐stimulated RAW 264.7 murine macrophage cells
Author(s) -
Lin YuHsien,
Lin YuJung,
Chang TingHsuan,
Chang YunHsuan,
Lim YunPing,
Chung JingGung,
Hsieh WenTsong
Publication year - 2020
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.23000
Subject(s) - chemistry , transcription factor , stat protein , protein kinase b , nitric oxide synthase , activator (genetics) , iκbα , tlr4 , microbiology and biotechnology , nf κb , signal transduction , stat3 , nitric oxide , biology , biochemistry , receptor , organic chemistry , gene
Although pipoxolan (PIPO) is a smooth muscle relaxant, its anti‐inflammatory capability has not been studied. Therefore, we investigated the anti‐inflammatory molecular mechanisms of PIPO in lipopolysaccharide (LPS)‐induced RAW 264.7 macrophages. In this study, we used the MTT assay to evaluate the cytotoxicity, applied the enzyme‐linked immunosorbent assay to determine the inflammatory cytokines, and performed Western blotting to assess protein expression. The results showed that PIPO significantly inhibited cytokine production, including nitric oxide, prostaglandin E 2 , tumor necrosis factor‐α, and interleukin‐6. PIPO also suppressed the pro‐inflammatory mediator expression with inducible nitric oxide synthase and cyclooxygenase‐2. Moreover, PIPO prohibited the multiple inflammatory transcription factor pathways, including inhibitor kappa B/nuclear factor of the κ light chain enhancer of B cells (NF‐κB), mitogen‐activated protein kinase/activator protein‐1 (AP‐1), Janus kinase/signal transducer and activator of transcription (STAT), and toll‐like receptor 4 (TLR4)/serine/threonine kinase (AKT). Besides, PIPO effectively activated the nuclear factor erythroid 2‐related factor 2 (Nrf2)/heme oxygenase‐1 antioxidative pathway. Collectively, PIPO may attenuate the inflammatory effects via influencing the LPS/TLR4 receptor binding; suppress the expression of anti‐inflammatory transcription factors NF‐κB, AP‐1, and STAT; and activating the antioxidative transcription factor Nrf2 in LPS‐stimulated mouse RAW 264.7 cells.