International immunopharmacology
-
Int. Immunopharmacol. · Apr 2014
Resveratrol prevents TNF-α-induced muscle atrophy via regulation of Akt/mTOR/FoxO1 signaling in C2C12 myotubes.
Muscle atrophy poses a serious concern to patients inflicted with inflammatory diseases. There is now increasing evidence which suggests a vital role for tumor necrosis factor alpha (TNF-α) in muscle pathology associated with impairment of differentiation and muscle wasting. Resveratrol has been an ascribed inhibitory effect on glucocorticoid-induced muscle atrophy in vitro, but the influence of resveratrol on the growth of C2C12 myotubes exposed to TNF-α remains unclear. ⋯ Resveratrol supplementation effectively counteracts TNF-α induced muscle protein loss and reverses declining expression of Akt, mTOR, p70S6K, 4E-BP1and FoxO1, but exerts no influence of FoxO3a expression. Our study demonstrates that resveratrol can reverse the muscle cell atrophy caused by TNF-α through regulation of the Akt/mTOR/FoxO1 signaling pathways, followed by inhibition of the atrophy-related ubiquitin ligase. Our findings suggested that resveratrol could represent a possible strategy to improve muscle mass.
-
Int. Immunopharmacol. · Mar 2014
Zingerone attenuates lipopolysaccharide-induced acute lung injury in mice.
Zingerone, one of the active components of ginger, is a phenolic alkanone with antioxidant and anti-inflammatory properties. In the present study, we analyzed the role of zingerone against RAW 264.7 cells and acute lung injury induced by lipopolysaccharide (LPS) in mice. RAW cells or BALB/c mice were pretreated with zingerone one hour before stimulated with LPS. ⋯ The lung wet-to-dry weight (W/D) ratios, as the index of pulmonary edema, were markedly decreased by zingerone pretreatment. Furthermore, we demonstrated that zingerone attenuates the mitogen-activated protein kinases (MAPK) and nuclear factor-kappaB (NF-κB) signaling pathways through blocking the phosphorylation of ERK, p38/MAPK and IκBα, NF-κB/P65. These results suggest that zingerone may provide protective effects against LPS-induced ALI.
-
Int. Immunopharmacol. · Feb 2014
A study on circadian rhythm disorder of rat lung tissue caused by mechanical ventilation induced lung injury.
Ventilator-induced lung injury (VILI), the most serious complication of mechanical ventilation therapy, is an excessive inflammatory response in lung tissue characterized by infiltration of inflammatory cells and overproduction of inflammatory mediators. The pathogenesis of VILI is very complex. It is becoming increasingly evident that disruption of circadian rhythm affects the immune response. ⋯ We found that Rev-erbα mRNA was significantly decreased in high tide volume mechanical ventilation group compared with spontaneous group, the same as REV-ERBα protein product which was tested by Western blot approach. Stimulation of REV-ERBα activity by SR9009 greatly diminished VILI-induced lung edema, inflammatory cell infiltration and the production of the pro-inflammatory cytokine TNF-α. Collectively, our findings are the first to show that REV-ERBα plays an important role in VILI and inflammation, and circadian rhythm disorder in inflammation response may be a novel pathogenesis of VILI.
-
Int. Immunopharmacol. · Feb 2014
Remission of food allergy by the Janus kinase inhibitor ruxolitinib in mice.
To clarify the role of Janus kinase (JAK) in and the efficacy of JAK inhibitors on food allergy, we investigated the effect of the clinically available JAK inhibitor ruxolitinib on mouse food allergy and the functions of cultured mast cells in vitro. Anaphylactic symptoms including diarrhea and decreases in body temperature pursuant to oral ovalbumin (OVA) challenges in food allergy mice were attenuated by the daily oral administration of ruxolitinib. This drug inhibited increases in mouse mast cell protease-1 concentrations in the serum and mast cell numbers in the intestines of these mice as well as degranulation, IL-13 production, and the spontaneous and IL-9-dependent survival of mouse bone marrow-derived mast cells in spite of the absence of an effect of ruxolitinib on passive systemic anaphylaxis. ⋯ Moreover, ruxolitinib administration to mice that had already exhibited anaphylactic responses to previous challenges reduced anaphylactic responses to further oral OVA challenges, which suggested that ruxolitinib has a therapeutic potential on food allergy. Our results showed that ruxolitinib remitted food allergy in mice mainly through immunosuppression and the prevention of mast cell hyperplasia, and partially through the inhibition of mast cell activation. We consider JAK inhibition to be a promising strategy for the prevention of food allergy, and ruxolitinib along with its derivatives inhibiting JAK as good candidates for therapeutic drugs to treat food allergy.
-
Int. Immunopharmacol. · Jan 2014
Aspirin-triggered lipoxin A4 attenuates lipopolysaccharide induced inflammatory response in primary astrocytes.
The activation of astrocytes contributes to inflammatory responses underlying brain injury and neurodegenerative diseases. Lipoxins have emerged as mediators of endogenous anti-inflammatory events. However, the involvement of aspirin-triggered-lipoxin A4 (ATL) in astrocyte-induced neuroinflammatory responses has not been investigated. ⋯ ATL also reduced the expression of cyclooxygenase 2 and inducible nitric oxide synthase mRNA and protein. Furthermore, ATL suppressed the LPS-induced translocation of the NF-κB p65 subunit to the nucleus and prevented LPS-induced IκBα phosphorylation in a dose-dependent manner. These findings suggest that ATL attenuates neuroinflammation by inhibiting the NF-κB signal transducer pathway in cultured cortical astrocytes.