@article{APS6483,
author = {Jun-xia Wang and Li-fei Hou and Yang Yang and Wei Tang and Ying Li and Jian-ping Zuo},
title = {SM905, an artemisinin derivative, inhibited NO and pro-inflammatory cytokine production by suppressing MAPK and NF-κB pathways in RAW 264.7 macrophages},
journal = {Acta Pharmacologica Sinica},
volume = {30},
number = {10},
year = {2016},
keywords = {},
abstract = {Aim: To elucidate the anti-inflammatory potentials and underlying mechanisms of SM905, a novel artemisinin derivative, in lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells.
Methods: Nitric oxide (NO) generation, cytokine production, and the protein expression levels of inducible nitric-oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were examined using a Griess assay, an enzyme-linked immunosorbent assay (ELISA) and a Western blotting assay, respectively. The mRNA expression was measured using real-time PCR. The phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2), p38, c-jun N-terminal kinase (JNK), and the degradation of IκBα were assessed by Western blotting analysis. The nuclear translocation of nuclear factor-κB (NF-κB) was observed using confocal microscopy.
Results: Pretreatment with SM905 (0, 0.1, 1, and 10 μmol/L) suppressed LPS-induced NO, TNF-α, IL-1β, and IL-6 production, and decreased both protein and mRNA levels of iNOS and COX-2. The mRNA expression of LPS receptor Toll-like receptor 4 (TLR4) and myeloid differentiation protein-2 (MD-2) was not changed, while LPS-induced CD14 expression was slightly reduced after SM905 treatment. SM905 markedly decreased the activation of ERK1/2, p38 and JNK suppressed the degradation of IκBα, but did not modify the expression of interferon regulatory factor-1 (IRF-1), signal transducer and activator of transcription 1 (STAT1) or interferon-inducible protein-10 (IP-10). By using confocal microscopy, we further observed that NF-κB was correspondingly inhibited in SM905-treated cells.
Conclusion: SM905 inhibited NO and pro-inflammatory cytokine production in LPS-stimulated RAW 264.7 cells and these effects are at least partially mediated through suppression of the MAPK and NF-κB signaling pathways.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/6483}
}