International immunopharmacology
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Int. Immunopharmacol. · Mar 2019
Peroxiredoxin 6 knockout aggravates cecal ligation and puncture-induced acute lung injury.
The aim of present study was to investigate the effects and mechanisms of peroxiredoxin (Prdx) 6 on cecal ligation and puncture (CLP) induced acute lung injury (ALI) in mice. ⋯ Prdx 6 knockout aggravated the CLP induced lung injury by augmenting oxidative stress, inflammation and matrix degradation partially through NF-κB pathway.
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Int. Immunopharmacol. · Mar 2019
Meta AnalysisEfficacy and safety of CTLA-4 inhibitors combined with PD-1 inhibitors or chemotherapy in patients with advanced melanoma.
Although immune checkpoint inhibitor monotherapy has demonstrated significant efficacy in advanced melanoma, no study has systematically evaluated the efficacy and safety of the combination regimens. In this study, we conduct a comprehensive meta-analysis to explore the efficacy and safety of CTLA-4 inhibitors combined with PD-1 inhibitors or chemotherapy in advanced melanoma. ⋯ Combination regimens significantly improved OS and PFS of advanced melanoma patients compared to monotherapy. An acceptable safety profile was observed in both CTLA-4 inhibitors plus PD-1 inhibitors and CTLA-4 inhibitors plus chemotherapy. A comparison of these two combination regimens showed that patients who received CTLA-4 inhibitors plus PD-1 inhibitors had a better therapeutic effect compared to those receiving CTLA-4 inhibitors plus chemotherapy. Further randomized clinical trials are urgently required to validate our results.
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Int. Immunopharmacol. · Mar 2019
Inhibition of macrophage migration inhibitory factor attenuates inflammation and fetal kidney injury in a rat model of acute pancreatitis in pregnancy.
Acute pancreatitis in pregnancy (APIP) is a severe disease during pregnancy that mostly occurs during the third trimester. It can lead to additional complications including preterm delivery and high fetal mortality. In this study, we investigated the protective effects of (S, R)-3-(4-hydroxyphenyl)-4, 5dihydro-5-isoxazole acetic methyl ester (ISO-1), an inhibitor of macrophage migration inhibitory factor (MIF), on fetal kidney injury associated with the maternal acute necrotizing pancreatitis (ANP) and its potential mechanisms in a rat model. ⋯ The results showed that fetal rats exhibited obvious acute kidney injury during APIP, and pregnant rats pretreated with ISO-1 notably attenuated the lesions. ISO-1 also significantly reduced the expression of MIF and the activations of p38MAPK, NF-κB, as well as the levels of TNF-α and IL-1β. These results indicated that ISO-1 could attenuate fetal kidney injury in pregnant rats with ANP by inhibiting MIF mediated p38MAPK/NF-κB signal pathways to reduce inflammatory response.
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Int. Immunopharmacol. · Feb 2019
Fraxin ameliorates lipopolysaccharide-induced acute lung injury in mice by inhibiting the NF-κB and NLRP3 signalling pathways.
Fraxin, the effective component of the Chinese traditional medicine Cortex Fraxini, is reported to have anti-inflammatory effects. This study assessed the anti-inflammatory effect of fraxin on the lipopolysaccharide (LPS)-induced inflammatory response in A549 cells and the protective efficacy on LPS-induced acute lung injury (ALI) in mice. Fraxin reduced LPS-induced TNF-α, IL-6 and IL-1β production in A549 cells and alleviated the LPS-induced wet/dry (W/D) weight ratio and the effects observed via histopathological examination of the lung in vivo. ⋯ Immunohistochemistry analysis showed that fraxin suppressed LPS-induced inflammatory damage. The expression of proteins involved in the NF-κB and NLRP3 inflammatory corpuscle signalling pathways was consistent between the lung tissues and cell samples. Overall, fraxin played a protective role in LPS-induced lung injury by inhibiting the NF-κB and NLRP3 signalling pathways.
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Int. Immunopharmacol. · Jan 2019
Quercetin inhibits Mrgprx2-induced pseudo-allergic reaction via PLCγ-IP3R related Ca2+ fluctuations.
An allergic reaction is a potentially fatal hypersensitivity response caused by mast cell activation, particularly histamine and lipid mediators. Histamine release caused by reaction to drugs is considered a pseudo-allergic reaction. Quercetin is known for its anti-allergic immune effect. ⋯ The docking results showed that Quercetin had a good binding affinity with Mrgprx2 similar to the one of Substance P and C48/80. Therefore, Quercetin inhibited Mrgprx2-induced pseudo-allergic reaction via PLCγ-IP3R associated Ca2+ fluctuations. Our results validated Quercetin as an effective small molecule inhibiting Mrgprx2-induced pseudo-allergic reaction via PLCγ-IP3R associated Ca2+ fluctuations, thus highlighting a potential candidate to suppress Mrgprx2 induced pseudo-allergic related diseases.