Resveratrol prevents hypoxia-induced retinal ganglion cell death related with ErbB2

AIM: To confirm the changes in proteins related with hypoxia-induced retinal cell death and to assess the effects of resveratrol(Res).METHODS: The therapeutic effect of Res was verified using an ischemic/reperfusion(I/R) model in vivo and a hypoxia modelin retinal ganglion cells(RGCs) in vitro.Death of RGCs were confirmed by TUNEL assay.Protein expression was confirmed by Western blotting and immunohistochemistry.In addition, flow cytometric analysis was used to confirm the response in the cell unit to obtain more accurate data.RESULTS: ErbB2 expression and apoptosis in the ganglion cell layer(GCL) increased after I/R injury.Treatment of Res rescued I/R-induced ganglion cell death, downregulated apoptosis and ErbB2 protein expression in the retina.In subsequent in vitro models, Res affects apoptosis by regulating the phosphorylation and expression of mouse double minute 2 homolog(MDM2), along with those of ErbB2.These results suggest that Res reverses GCL-specific apoptosis via downregulation of ErbB2 in ischemic injury.CONCLUSION: In light of Res favorable properties, it should be evaluated in the treatment of RGC death and related retinal disease characterized by ErbB2 and MDM2 expression.Therefore, Res is appropriate therapeutic agent for treating ischemic injury-related eye diseases by targeting the expression of ErbB2 and MDM2.

Carbon monoxide decreases interleukin-1β levels in the lung through the induction of pyrin

Carbon monoxide （CO） can act as an anti-inflammatory effector in mouse models of lung injury and disease, through the downregulation of pro-inflammatory cytokines production, though the underlying mechanisms remain unclear. The nucleotide-binding oligomerization domain-, leucine-rich region-, and pyrin domain-containing-3 （NLRP3） inflammasome is a protein complex that regulates the maturation and secretion of pro-inflammatory cytokines, including interleukin-1β （IL-1β）. In this report, we show that the CO-releasing molecule （CORM-2） can stimulate the expression of pyrin, a negative regulator of the NLRP3 inflammasome. CORM-2 increased the transcription of pyrin in the human leukemic cell line （THP-1） in the absence and presence of lipopolysaccharide （LPS）. In THP-1 cells, CORM-2 treatment dose-dependently reduced the activation of caspase-1 and the secretion of IL-lp, and increased the levels of IL-IO, in response to LPS and adenosine 5＇-triphosphate （ATP）, an NLRP3 inflammasome activation model. Genetic interference of IL-10 by small interfering RNA （siRNA） reduced the effectiveness of CORM-2 in inhibiting IL-1β production and in inducing pyrin expression. Genetic interference of pyrin by siRNA increased IL-lp production in response to LPS and ATP, and reversed CORM-2-dependent inhibition of caspase-1 activation. CO inhalation （250 ppm） in vivo increased the expression of pyrin and IL-10 in lung and spleen, and decreased the levels of IL-1β induced by LPS. Consistent with the induction of pyrin and IL-10, and the downregulation of lung IL-1β production, CO provided protection in a model of acute lung injury induced by intranasal LPS administration. These results provide a novel mechanism underlying the anti-inflammatory effects of CO, involving the IL-10-dependent upregulation of pyrin expression.