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.
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Acknowledgements
This work was supported by a grant from Shanghai Science and Technology Committee (No 06DZ19006) and the Knowledge Innovation Program of the Chinese Academy of Sciences (No SIMM0709QN-01).
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Wang, Jx., Hou, Lf., Yang, Y. et al. SM905, an artemisinin derivative, inhibited NO and pro-inflammatory cytokine production by suppressing MAPK and NF-κB pathways in RAW 264.7 macrophages. Acta Pharmacol Sin 30, 1428–1435 (2009). https://doi.org/10.1038/aps.2009.138
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DOI: https://doi.org/10.1038/aps.2009.138
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