[4i, a novel PPARγ ligand, inhibits the production of inflammatory cytokines in murine macrophages by blocking NF-κB and MAPK pathway]

Autor: Fang, Wang, Jin, Jiang, Lin, Xia, Jian, Lyu, Changyu, Cai, Bingchang, Xin
Rok vydání: 2018
Předmět:
Zdroj: Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology. 34(6)
ISSN: 1007-8738
Popis: Objective To investigate the anti-inflammatory activity and mechanism of peroxisome proliferator activated receptor gamma (PPARγ) ligand 4i. Methods Mouse macrophages RAW264.7 at the logarithmic phase were induced by 100 ng/mL lipopolysaccharide (LPS). The effect of 4i (10 μmol/L) on the production of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) was investigated by ELISA. The effect of 4i on the protein levels of nuclear factor κB (NF-κBp65), IκBα, JNK, ERK1/2, p38MAPK were detected by Western blot analysis. Furthermore, the role of PPARγ in the regulation of inflammatory-related NF-κB and MAPK signaling pathways was analyzed using GW9662 (5 μmol/L) which was a highly irreversible PPARγ antagonist. And the docking analysis was carried out using SYBYL 8.1 software to investigate the binding interaction of 4i with PPARγ ligand. Results The 4i significantly decreased the production of TNF-α and IL-6 in a time-dependent manner. It also inhibited the phosphorylation of NF-κBp65, IκBα, JNK, ERK1/2 and p38MAPK in varying degrees, and the suppressive effect of 4i could be reversed by GW9662. The 4i exhibited a strong binding ability with PPARγ. Conclusion The anti-inflammation effect of 4i was due to the interaction with PPARγ, thereby suppressing the activation of NF-κB and MAPK cascades and resulting in the decreased levels of TNF-α and IL-6.
Databáze: OpenAIRE