Pharmacological Research 103 (2016) 114–122 Contents lists available at ScienceDirect Pharmacological Research j ourna l h o mepa ge: www.elsevier.com/l ocate/yphrs Role of adiponectin in sphingosine-1-phosphate induced airway hyperresponsiveness and inflammation Ersilia Nigro a,1 , Maria Matteis b,1 , Fiorentina Roviezzo c , Valentina Mattera Iacono c , Olga Scudiero a,d , Giuseppe Spaziano b , Gioia Tartaglione b , Konrad Urbanek b , Rosanna Filosa b , Aurora Daniele a,e , Bruno D’Agostino b,∗ a CEINGE-Advanced Biotechnology s.c.ar.l, Naples, Italy b Department of Experimental Medicine, Second University of Naples, Naples, Italy c Department of Experimental Pharmacology, University Federico II of Naples, Naples, Italy d Department of Molecular Medicine and Medical Biotechnology, University Federico II of Naples, Naples, Italy e Department of Environmental Sciences and Technologies Biological and Pharmaceutical, Second University of Naples, Caserta, Italy a r t i c l e i n f o Article history: Received 4 August 2015 Received in revised form 24 September 2015 Accepted 5 October 2015 Available online 20 October 2015 Chemical compounds studied in this article: Sphingosine 1-phosphate (PubChem CID: 5283560) Keywords: Airway hyperresponsiveness Inflammation S1P Adiponectin Adiponectin receptors a b s t r a c t Epidemiological data suggest that obesity represent an important risk factor for asthma, but the link between excess fat and airway hyperresponsiveness (AHR) and inflammation is not fully understood. Recently, a key role in physiopathologic conditions of lungs has been given to adiponectin (Acrp30). Acrp30 is one of the most expressed adipokines produced and secreted by adipose tissue, showing an intriguing relationship with metabolism of sphingolipids. Sphingosine-1-phosphate (S1P) has been proposed as an important inflammatory mediator implicated in the pathogenesis of airway inflamma- tion and asthma. In the present study we analyze the effects of recombinant Acrp30 administration in an experimental model of S1P-induced AHR and inflammation. The results show that S1P is able to reduce endogenous Acrp30 serum levels and that recombinant Acrp30 treatment significantly reduce S1P-induced AHR and inflammation. Moreover, we observed a reduction of Adiponectin receptors (Adi- poR1, AdipoR2 and T-cadherin) expression in S1P treated mice. Treatment with recombinant Acrp30 was able to restore Acrp30 serum levels and adiponectin receptors expression. These results could indicate the ability of S1P to modulate the Acrp30 action, by modulating not only the serum levels of the protein, but also its receptors. Taken together, these data suggest that adiponectin could represent a possible biomarker in obesity-associated asthma. © 2015 Elsevier Ltd. All rights reserved. 1. Introduction Asthma has been viewed for a long time as a single disease entity, but currently it is considered a syndrome characterized by inter- mittent airway obstruction, bronchial hyperreactivity and chronic airway inflammation [1]. The rapid increase of asthma prevalence in recent years has a considerable impact on public health. Fur- thermore, obesity represents a risk factor not only for the onset but also for the severity of asthma in adult as well as in children ∗ Corresponding author at: Department of Experimental Medicine, Section of Pharmacology, Second University of Naples, via Costantinopoli 16, 80136 Naples, Italy. E-mail address: bruno.dagostino@unina2.it (B. D’Agostino). 1 These authors have equally contributed to this work. [2–5]. Until now, the link between excess fat and asthma is not fully understood but deregulation of adipokines secretion by adi- pose tissue plays a crucial role [6]. Adiponectin (Acrp30) is one of the most expressed adipokines produced and secreted by adipose tissue. Acrp30 plays a key role in metabolic and inflammatory dis- orders [6]; recently, a role for Acrp30 has been evidenced also in physio-pathologic conditions of lung [7]. In vivo, excess fat induces airway hyperresponsiveness (AHR), enhances allergen or ozone- induced AHR [8] but the precise mechanisms linking obesity with airway inflammation and AHR have not been understood. Acrp30 acts through its receptors (AdipoR1 and AdipoR2 and T-cadherin) widely expressed in several organs, tissues and cell lines [9–11]. Recently, an intriguing potential relationship has been evidenced between Acrp30 and metabolism of sphingolipids. Both AdipoR1 and AdipoR2 stimulate ceramidase to degrade ceramide to sphin- gosine, converting it into sphingosine 1-phosphate (S1P). S1P has http://dx.doi.org/10.1016/j.phrs.2015.10.004 1043-6618/© 2015 Elsevier Ltd. All rights reserved.