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.
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Int. Immunopharmacol. · Mar 2015
Anti-inflammation effect of methyl salicylate 2-O-β-D-lactoside on adjuvant induced-arthritis rats and lipopolysaccharide (LPS)-treated murine macrophages RAW264.7 cells.
Methyl salicylate 2-O-β-D-lactoside (MSL) is a derivative of natural salicylate isolated from Gaultheria yunnanensis (Franch.) Rehder, which is widely used for treating rheumatoid arthritis (RA), swelling and pain. The aim of the present study was to investigate the effect of MSL on the progression of adjuvant-induced arthritis (AIA) in rat in vivo and explore the anti-inflammatory effects and mechanism of MSL in lipopolysaccharide (LPS)-treated murine macrophages RAW264.7 cells in vitro. Our results showed that MSL significantly inhibited the arthritis progression in AIA rats, decreasing the right hind paw swelling and ankle diameter, attenuating histopathological changes and suppressing the plasma levels of TNF-α and IL-1β in AIA rats. ⋯ MSL dose-dependently inhibited the activity of COX-1, and COX-2. Moreover, MSL prominently inhibited LPS-induced activation of MAPK in RAW264.7 cells by blocking phosphorylation of p38 and ERK. Our study suggests that MSL may be effective in the treatment of inflammatory diseases by inhibiting the pro-inflammatory cytokine production and regulating the MAPK signal pathway.
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Int. Immunopharmacol. · Jan 2015
New compound, 5-O-isoferuloyl-2-deoxy-D-ribono-γ-lacton from Clematis mandshurica: Anti-inflammatory effects in lipopolysaccharide-stimulated BV2 microglial cells.
Microglia are main immune cells to exacerbate neural disorders in persistent overactivating. Therefore, it is a good strategy to regulate microglia for the treatment of neural disorders. In the present study, we isolated and characterized a novel compound, 5-O-isoferuloyl-2-deoxy-D-ribono-γ-lacton (5-DRL) from Clematis mandshurica, and evaluated its anti-inflammatory effect in lipopolysaccharide (LPS)-treated BV2 microglial cells. 5-DRL inhibited the expression of LPS-stimulated proinflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2), as well as their regulatory genes inducible NO syntheses (iNOS) and cyclooxygenase-2 (COX-2). 5-DRL also downregulated the LPS-induced DNA-binding activity of nuclear factor-κB (NF-κB) through suppression of the nuclear translocation of the NF-κB subunits, p65 and p50. ⋯ The present study also indicated that 5-DRL suppresses NO and PGE2 production by inducing heme oxygenase-1 (HO-1) via nuclear factor erythroid 2-related factor 2 (Nrf2). Taken together, the present data indicate that 5-DRL attenuates the production of proinflammatory mediators such as NO and PGE2 as well as their regulatory genes in LPS-stimulated BV2 microglial cells by inhibiting ROS-dependent NF-κB activation and stimulating the Nrf2/HO-1 signal pathway. These data may be implicated in the application of 5-DRL in LPS-stimulated inflammatory disease.