title: Adiponectin affects lung epithelial A549 cell viability counteracting TNFα and IL-1ß toxicity through AdipoR1.
abstract: 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 TNFα and/or IL-1ß, two potent lung inflammatory cytokines. We showed that Acrp30, in dose- and time-dependent manner, reduces cytotoxic effects of TNFα and/or IL-1ß improving cell viability and decreasing apoptosis. In addition, Acrp30 inhibits NF-κB 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-κB 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.
authors.affiliation: CEINGE-Biotecnologie Avanzate Scarl, Naples, Italy.
authors.forename: Ersilia
authors.initials: E
authors.lastname: Nigro
authors.forename: Olga
authors.initials: O
authors.lastname: Scudiero
authors.forename: Daniela
authors.initials: D
authors.lastname: Sarnataro
authors.forename: Gennaro
authors.initials: G
authors.lastname: Mazzarella
authors.forename: Matteo
authors.initials: M
authors.lastname: Sofia
authors.forename: Andrea
authors.initials: A
authors.lastname: Bianco
authors.forename: Aurora
authors.initials: A
authors.lastname: Daniele
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000235:genetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: C499918:ADIPOQ protein, human; C475418:ADIPOR1 protein, human; D052242:Adiponectin; C508585:IL1B protein, human; D053583:Interleukin-1beta; D054419:Receptors, Adiponectin; D014409:Tumor Necrosis Factor-alpha; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3