International immunopharmacology
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Int. Immunopharmacol. · Dec 2012
Imbalance of Th17/Treg cells in mice with chronic cigarette smoke exposure.
Recent studies have revealed that autoimmune responses mediated by CD4(+) T cells may contribute to the development of chronic obstructive pulmonary disease (COPD). Meanwhile, imbalance of Th17/Treg has been reported to play a key role in the pathogenesis of autoimmune diseases. However, information on Th17/Treg balance in COPD is relatively limited. ⋯ Our study thus reveals that the Th17/Treg imbalance exists in mice with chronic CS exposure, suggesting its potential role in the breakdown of immune self-tolerance in COPD. Further research on regulation of Th17/Treg balance may provide insights into the development of new therapeutic targets for this disease.
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Int. Immunopharmacol. · Dec 2012
Alantolactone suppresses inducible nitric oxide synthase and cyclooxygenase-2 expression by down-regulating NF-κB, MAPK and AP-1 via the MyD88 signaling pathway in LPS-activated RAW 264.7 cells.
Several sesquiterpene lactones are the active components of several medicinal plants and have been demonstrated to perform various pharmacological functions. In this study, we investigated the anti-inflammatory effects of alantolactone, a sesquiterpene lactone isolated from the root of Aucklandia lappa, in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and peritoneal macrophages. Alantolactone inhibited inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) protein and mRNA transcription, as well as the downstream products, nitric oxide (NO), prostaglandin E(2) (PGE(2)) and tumor necrosis factor-α (TNF-α). ⋯ A further study indicated that alantolactone attenuated the phosphorylation of Akt and inhibited the expression of MyD88 and Toll-interleukin 1 receptor domain-containing adaptor protein (TIRAP), an upstream signaling molecule required for IKK and MAPKs activation. Taken together, these results suggest that alantolactone exerts its anti-inflammatory effect in LPS-stimulated RAW 264.7 cells by suppressing NF-κB activation and MAPKs phophorylation via downregulation of the MyD88 signaling pathway. Thus, alantolactone may provide a useful therapeutic approach for inflammation-associated diseases.