International immunopharmacology
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Int. Immunopharmacol. · Apr 2015
Protection against reperfusion lung injury via aborgating multiple signaling cascades by trichostatin A.
Trichostatin A (TSA) is a histone deacetylase inhibitor with anti-inflammatory effects. Nonetheless, little information is available about the effect of TSA in ischemia-reperfusion (IR)-induced lung injury. In a perfused rat lung model, IR was induced by 40min of ischemia followed by 60min of reperfusion. ⋯ Furthermore, TSA attenuated the phosphorylation of extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase, degradation of the inhibitor of nuclear factor (NF)-κB, and nuclear NF-κB levels. TSA also decreased poly (ADP-ribose) polymerase but enhanced acetylated histone H3 acetylation, Bcl-2, and mitogen-activated protein kinase phosphatase-1 (MKP-1) expression in IR lung tissue. Therefore, TSA exerted a protective effect on IR-induced lung injury via increasing histone acetylation and MKP-1 protein expression, repressing NF-κB, mitogen-activated protein kinase, and apoptosis signaling pathways.
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Int. Immunopharmacol. · Apr 2015
Clinical TrialDendritic cell immunotherapy combined with cytokine-induced killer cells promotes skewing toward Th2 cytokine profile in patients with metastatic non-small cell lung cancer.
Dendritic cell (DC) vaccination and cytokine-induced killer (CIK) cell therapy (DC/CIK) have shown limited success in the treatment of advanced non-small cell lung cancer (NSCLC). To investigate the reason for this limited success, the effects of DC/CIK cell therapy on the immune responses of tumor-bearing patients and patients with resected NSCLC were evaluated. In the total 50 patients studied, the serum concentrations of the Th2 cytokines (IL-4 and IL-10) in tumor-bearing patients were significantly higher than those with resected NSCLC before immunotherapy. ⋯ Furthermore, overproduction of vascular endothelial growth factor (VEGF) in tumor-bearing patients showed a statistically positive correlation with IL-4, suggesting that VEGF might be responsible for the predominance of serum Th2 cytokines. In a word, tumor-bearing patients developed a Th2-dominant status that could not be reversed toward Th1 following immunotherapy. A combined regiment of DC vaccination and CIK cell therapy with other treatments to overcome systemic Th2-dominant immune response might improve the current clinical benefit.
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Int. Immunopharmacol. · Apr 2015
Anti-inflammatory activities of cardamonin from Alpinia katsumadai through heme oxygenase-1 induction and inhibition of NF-κB and MAPK signaling pathway in the carrageenan-induced paw edema.
Cardamonin is a chalcone isolated from Alpinia katsumadai. This study is aimed to evaluate treatment of cardamonin decreased the paw edema at the 5th hour after λ-carrageenan (Carr) administration and increased the activities of catalase (CAT) and superoxide dismutase (SOD) in the anti-inflammatory test. ⋯ Western blotting revealed that cardamonin decreased Carr-induced inducible nitric oxide synthase (iNOS), cycloxyclase (COX-2), nuclear factor-κB (NF-κB) and MAPK [extracellular signal-regulated protein kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), p38] expressions and increased heme oxygenase-1 (HO-1) expressions at the 5th hour in the edema paw. The anti-inflammatory mechanisms of cardamonin might be related to the decrease in the level of MDA, iNOS, COX-2, NF-κB, and MAPK and induction of the HO-1 expression in the edema paw via increasing the activities of CAT and SOD in the edema paw through the suppression of NO, TNF-α, IL-1β, and IL-6.