title: Bezafibrate, a peroxisome proliferator-activated receptor α agonist, decreases circulating CD14(+)CD16(+) monocytes in patients with type 2 diabetes.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Koshigaya Hospital, Dokkyo Medical University, Koshigaya, Saitama, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Terasawa
authors.affiliation: Department of Endocrinology and Metabolism, Dokkyo Medical University, Mibu, Tochigi, Japan. Electronic address: yaso@dokkyomed.ac.jp.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Aso
authors.affiliation: Department of Molecular Genetic Testing, Joint Research Center, Koshigaya Hospital, Dokkyo Medical University, Koshigaya, Saitama, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Omori
authors.affiliation: Mitsubishi Chemical Medience Corporation, Itabashi, Tokyo, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Fukushima
authors.affiliation: Mitsubishi Chemical Medience Corporation, Itabashi, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Momobayashi
authors.affiliation: Department of Internal Medicine, Koshigaya Hospital, Dokkyo Medical University, Koshigaya, Saitama, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Inukai
mesh_terms: D000328:Adult; D001629:Bezafibrate / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D018149:Glucose Intolerance / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000145:classification / Q000187:drug effects* / Q000276:immunology; D047493:PPAR alpha / Q000819:agonists*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism; D057170:Translational Research, Biomedical
chemical_list: D016207:Cytokines; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D018836:Inflammation Mediators; D018950:Lipopolysaccharide Receptors; D047493:PPAR alpha; D012333:RNA, Messenger; D017452:Receptors, IgG; D001629:Bezafibrate