BML-111 attenuats acute lung injury induced by intestine ischemia-reperfusion via inhibiting p38 MAPK/NF-κB signaling pathway / 实用医学杂志

Objective This study aims to investigate the effect of Lipoxin A4 receptor on acute lung injury (ALI) induced by intestine ischemia-reperfusion (IIR). Methods Thirty-two 8-week old SD rats were randomly divided into four groups: sham, intestine ischemia-reperfusion (IIR), IIR + BML111 (BML-111), Boc-2 + IIR +BML111 (Boc-2). BML-111 (1 mg/kg) was given intraperitoneally at the onset of reperfusion in the BML-111 and the Boc-2 group. Boc-2 (50 μg/kg) was given intraperitoneally after anesthesia in the Boc-2 group. Rats were subjected to superior mesenteric artery occlusion consisting of 45-min ischemia and 6-h reperfusion, and the sham laparotomy was served as controls. The lung pathology was assayed by the H&E staining. Lung water content was detected using dry/wet ratio. Concentrations of TNF-α, IL-1β, and IL-6 in lung tissue were determined by ELISA. The protein expression of p38 MAPK and NF-κB of lung was assayed by western blot. Results IIR induced serious ALI, with poor lung pathology and increased lung water content, elevation of TNF-α, IL-1β, and IL-6 levels in lung, accompanied with activation of p38 MAPK/NF-κB pathway. However, BML-111 could inhibit the activation of p38 MAPK/NF-κB pathway, leading to the reductions of TNF-α, IL-1β, and IL-6 in lung and attenuation of IIR-induced ALI. Conclusion BML-111 treatment could attenuate inflammation in lung after IIR injury via inactivating the p38 MAPK/NF-κB signaling pathway.

Effect of LX A4 and BML-111 on TLR4/NF-κB signaling pathway in macrophage / 实用医学杂志

Objective To determine the effect of lipoxins (LX) A4 and its agonist (BML-111) on the survival of RAW264.7 macrophage cells and TLR4/NF-κB signaling pathway. Methods RAW264.7 cells were treated with different concentrations of LPS, then the effect of LX A4 and BML-111 on the survival rate of these cells was observed. Cytotoxicity were detected by CCK-8 method and RT-PCR was used to detect the TLR4 and TRAF6 mRNA. The protein levels of TLR4 and pNF-κB p65 in RAW264.7 were determined by Western Blot. Results The survival rates of macrophage treated with LPS for 6 h in 1 000 ng/mL LPS in LX A4 group and BML-111 group were significantly higher than that in control group (P 0.05). Conclusion LX A4 and BML-111 could inhibit the cytotoxicity of LPS on the RAW264.7 macrophage cells through the inhibition of the activation of TLR4/NF-κB signaling pathway, then reduce the inflammation. And this stable BML-111 may appear as another promising treatment for IBD disease.

BML-111, the analogue of lipoxin, inhibits Hela cell proliferation / 实用医学杂志

Objective To investigate the effect of BML-111 (the analogue of lipoxin) on uterine Hela cell (cervix cancer cell line) proliferation and the underlying mechanism. Methods Hela cells were stimulated by 50, 100, 200 and 400 μg/L BML-111, respectively, and cell viability was determined by MTT assay. Hela cells were divided into three groups:the control group (no treatment), the BML-111(200μg/L) group and the BML-111(200μg/L)plus Boc-2 (10μmol/L)group. Expression and location of P53 protein were detected by immunofluorescence. Expressions of NF-κB p65,P53 and CyclinD1 protein were detected by Western blotting. Results BML-111 (100, 200 and 400 μg/L) could effectively inhibit Hela cell viability compared with the control group (P < 0.05). P53 expression was shown decreased in both the nucleus and the cytoplasm without any change of P53 location , however, Boc-2 could reverse this effect. BML-111 could effectively inhibit P53 and CyclinD1 expression via NF-κB pathway and the effects could also be inhibited by Boc-2. Conclusions BML-111 can effectively inhibit Hela cell proliferation via FPR2 and NF-κB pathway.