Adiponectin affects lung epithelial A549 cell viability counteracting TNFa and IL-1ß toxicity through AdipoR1

Adiponectin (Acrp30) exerts protective functions on metabolic and cellular processes as energy metabolism, cell proliferation and differentiation by two widely expressed receptors, AdipoR1 and AdipoR2. To date, the biological role of Acrp30 in lung has not been completely assessed but altered levels of Acrp30 and modulated expression of both AdipoRs have been related to establishment and progression of chronic obstructive pulmonary disease (COPD) and lung cancer. Here, we investigated the effects of Acrp30 on A549, a human alveolar epithelial cell line, showing how, in a time and dose-dependent manner, it decreases cell viability and increases apoptosis through ERK1/2 and AKT. Furthermore, we examined the effects of Acrp30 on A549 cells exposed to TNFa and/or IL-1ß, two potent lung inflammatory cytokines. We showed that Acrp30, in dose- and time-dependent manner, reduces cytotoxic effects of TNFa and/or IL-1ß improving cell viability and decreasing apoptosis. In addition, Acrp30 inhibits NF-?B nuclear trans-activation and induces the expression of the anti-inflammatory IL-10 cytokine without modifying that of pro-inflammatory IL-6, IL-8, and MCP-1 molecules via ERK1/2 and AKT. Finally, specifically silencing AdipoR1 or AdipoR2, we observed that NF-?B inhibition is mainly mediated by AdipoR1. Taken together, our data provides novel evidence for a direct effect of Acrp30 on the proliferation and inflammation status of A549 cells strongly supporting the hypothesis for a protective role of Acrp30 in lung. Further studies are needed to fully elucidate the Acrp30 lung effects in vivo but our results confirm this adipokine as a promising therapeutic target in lung diseases. © 2013 Elsevier Ltd. Adiponectin (Acrp30) exerts protective functions on metabolic and cellular processes as energy metabolism, cell proliferation and differentiation by two widely expressed receptors, AdipoR1 and AdipoR2. To date, the biological role of Acrp30 in lung has not been completely assessed but altered levels of Acrp30 and modulated expression of both AdipoRs have been related to establishment and progression of chronic obstructive pulmonary disease (COPD) and lung cancer. Here, we investigated the effects of Acrp30 on A549, a human alveolar epithelial cell line, showing how, in a time and dose-dependent manner, it decreases cell viability and increases apoptosis through ERK1/2 and AIM Furthermore, we examined the effects of Acrp30 on A549 cells exposed to TNF alpha and/or IL-1 beta, two potent lung inflammatory cytokines. We showed that Acrp30, in dose- and time-dependent manner, reduces cytotoxic effects of TNF alpha and/or IL-1 beta improving cell viability and decreasing apoptosis. In addition, Acrp30 inhibits NF-kappa B nuclear trans-activation and induces the expression of the anti-inflammatory IL-10 cytokine without modifying that of pro-inflammatory IL-6, IL-8, and MCP-1 molecules via ERK1/2 and ART. Finally, specifically silencing AdipoR1 or AdipoR2, we observed that NF-kappa B inhibition is mainly mediated by AdipoR1. Taken together, our data provides novel evidence for a direct effect of Acrp30 on the proliferation and inflammation status of A549 cells strongly supporting the hypothesis for a protective role of Acrp30 in lung. Further studies are needed to fully elucidate the Acrp30 lung effects in vivo but our results confirm this adipokine as a promising therapeutic target in lung diseases. (C) 2013 Elsevier Ltd. All rights reserved.