Adipocyte P2X7 receptors expression: A role in modulating inflammatory response in subjects with metabolic syndrome?

• Published in: Atherosclerosis Vol. 219; no. 2; pp. 552 - 558
• Main Authors: Madec, Stephanie, Rossi, Chiara, Chiarugi, Massimo, Santini, Eleonora, Salvati, Antonio, Ferrannini, Ele, Solini, Anna
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.12.2011; Elsevier
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology; adenosine triphosphate; Adenosine Triphosphate - analogs & derivatives; Adenosine Triphosphate - pharmacology; Adipocyte; adipocytes; Adipocytes - drug effects; Adipocytes - immunology; Adipocytes - metabolism; adipose tissue; Aged; atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blotting, Western; calcium; Calcium Signaling; Cardiology. Vascular system; Cardiovascular; Case-Control Studies; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique; fluorometry; gene expression; gene silencing; Humans; Inflammasome; Inflammasomes - metabolism; Inflammation; Inflammation - genetics; Inflammation - immunology; Inflammation - metabolism; Inflammation Mediators - blood; interleukin-6; Interleukin-6 - blood; Interleukin-6 - genetics; Intra-Abdominal Fat - drug effects; Intra-Abdominal Fat - immunology; Intra-Abdominal Fat - metabolism; Italy; Medical sciences; messenger RNA; Metabolic syndrome; Metabolic Syndrome - genetics; Metabolic Syndrome - immunology; Metabolic Syndrome - metabolism; Middle Aged; P2X7 receptor; patients; plasma membrane; Plasminogen Activator Inhibitor 1 - blood; Plasminogen Activator Inhibitor 1 - genetics; Purinergic P2X Receptor Agonists - pharmacology; Purinergic P2X Receptor Antagonists - pharmacology; Real-Time Polymerase Chain Reaction; receptors; Receptors, Purinergic P2X7 - drug effects; Receptors, Purinergic P2X7 - genetics; Receptors, Purinergic P2X7 - metabolism; Reverse Transcriptase Polymerase Chain Reaction; risk; RNA Interference; RNA, Messenger - metabolism; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Subcutaneous Fat - drug effects; Subcutaneous Fat - immunology; Subcutaneous Fat - metabolism; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - blood; Tumor Necrosis Factor-alpha - genetics; Up-Regulation; Western blotting; Adipocyte; Inflammation; Inflammasome; Metabolic syndrome; P2X7 receptor; P2X 7 receptor; Endocrinopathy; Vascular disease; Human; receptor; Atherosclerosis; P2X; Metabolic diseases; Cardiovascular disease
• ISSN: 0021-9150; 1879-1484; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2011.09.012

P2X7 receptor (P2X7R), upon its stimulation with extracellular ATP, modulates several inflammatory responses in different cell types. No information is available on its presence in human adipocytes and its potential involvement in the chronic inflammation associated with metabolic syndrome (MS). Therefore, we evaluated P2X7R presence and functional activity in adipocytes from visceral (VAT) and subcutaneous (SAT) adipose tissue of patients with MS and controls (CTL). Adipocyte gene expression of TNFα, IL-6 and PAI-1 (by realtime-PCR) and their plasma concentrations (ELISA); P2X7R expression (realtime-PCR, Western blot and immunofluorescence); P2X7R functional activity (intracellular calcium fluxes by fluorimetry); cytokine release from adipocytes (ELISA). The inflammasome components were also determined. In VAT, TNFα, IL-6 and PAI-1 were more expressed in MS than in CTL. These differences were confirmed in SAT for IL-6 and PAI-1. Plasma IL-6, PAI-1 and TNFα levels were higher in MS. P2X7R mRNA and protein, identified in both VAT and SAT, were more abundant in MS than in CTL. Immunofluoresce confirmed the typical “ring-like” arrangement of P2X7R at the plasma membrane. Benzoyl-benzoyl-ATP raised intracellular calcium both in VAT and SAT, and induced IL-6, TNFα and PAI-1 release in both MS and CTL cells. This effect was partially inhibited by KN62, specific human P2X7R blocker, or by P2X7R gene silencing. The inflammasome was more activated in MS than in CTL adipocytes. Human adipocytes express functionally active P2X7R, which modulate the release of inflammatory cytokines, at least in part via inflammasome activation. Adipocytes from MS patients show an enhanced P2X7R expression, which might contribute to the subclinical inflammatory status characterizing these patients and conferring them an increased CV risk.