Bezafibrate, a peroxisome proliferator–activated receptor α agonist, decreases circulating CD14+CD16+ monocytes in patients with type 2 diabetes

• Published in: Translational research : the journal of laboratory and clinical medicine Vol. 165; no. 2; pp. 336 - 345
• Main Authors: Terasawa, Tomoko, Aso, Yoshimasa, Omori, Kyoko, Fukushima, Maiko, Momobayashi, Atsushi, Inukai, Toshihiko
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2015
• Subjects: Adult; Bezafibrate - therapeutic use; Cross-Sectional Studies; Cytokines - metabolism; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - immunology; Female; Gene Expression - drug effects; Glucose Intolerance - blood; Glucose Intolerance - drug therapy; Glucose Intolerance - immunology; GPI-Linked Proteins - genetics; GPI-Linked Proteins - metabolism; Humans; Inflammation Mediators - metabolism; Internal Medicine; Lipopolysaccharide Receptors - metabolism; Male; Middle Aged; Monocytes - classification; Monocytes - drug effects; Monocytes - immunology; PPAR alpha - agonists; Receptors, IgG - genetics; Receptors, IgG - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Translational Medical Research; NGT; IL; PPAR; MNCs; TNF; IGT; mononuclear cells; normal glucose tolerance; tumor necrosis factor; impaired glucose tolerance; peroxisome proliferator-activated receptor; interleukin
• ISSN: 1931-5244; 1878-1810; 1878-1810
• DOI: 10.1016/j.trsl.2014.07.008

CD14+CD16+ monocytes are proinflammatory cells that produce tumor necrosis factor and interleukin (IL)-1β. The number of circulating CD14+CD16+ monocytes is increased in patients with chronic renal failure or coronary artery disease. We investigated the effect of bezafibrate, a peroxisome proliferator–activated receptor α agonist, on circulating CD14+CD16+ monocytes in patients with type 2 diabetes. Using cells isolated from type 2 diabetic subjects, we also examined the in vitro expression of CD16 messenger RNA (mRNA) by mononuclear cells (MNCs) exposed to bezafibrate. The percentage of CD14+CD16+ monocytes among all CD14+ monocytes was significantly higher in subjects with impaired glucose tolerance (P < 0.01) or type 2 diabetes (P < 0.05) than in those with normal glucose tolerance. The percentage of CD14+CD16+ monocytes was significantly lower in patients with type 2 diabetes who were taking bezafibrate (400 mg/d) than in patients not taking it (P < 0.01). Treatment with bezafibrate for 12 weeks significantly reduced the percentage of circulating CD14+CD16+ monocytes from 45.4 ± 25.2% to 38.3 ± 21.8% (P = 0.0144). In an in vitro study, the expression of CD16 mRNA by MNCs from 6 diabetic subjects was decreased after 24 hours of treatment with 10 μg/mL of bezafibrate (P < 0.05). Expression of IL-1β mRNA by MNCs was also decreased after 24 hours of treatment with 10 μg/mL of bezafibrate, whereas the IL-1β level in the culture supernatant was significantly decreased after treatment of MNCs with either 1 or 10 μg/mL of bezafibrate. In conclusion, bezafibrate decreased circulating CD14+CD16+ monocytes in patients with type 2 diabetes, probably by inhibiting the expression of CD16 mRNA.