title: Linagliptin Has Wide-Ranging Anti-Inflammatory Points of Action in Human Umbilical Vein Endothelial Cells.
abstract: BACKGROUND
  Because of the potential anti-inflammatory effects, linagliptin, a therapeutic dipeptidyl peptidase-4 inhibitor, is used as an effective drug for diabetic patients for whom inflammation is a prognosis-related factor. We investigated the anti-inflammatory mechanism of linagliptin using seven markers.
  
  
  METHODS
  We pretreated human umbilical vein endothelial cells (HUVECs), with linagliptin and lipopolysaccharide (LPS). The cytosolic fractions were evaluated for protein kinase A (PKA), protein kinase B (PKB), protein kinase C (PKC), ratio of reactive oxygen species (ROS) and Cu/Zn superoxide dismutase (SOD), activator protein 1 (AP-1), and adenosine 3',5'-cyclic monophosphate (cAMP).
  
  
  RESULTS
  Linagliptin increased the PKA and PKC activities and the cAMP levels in LPS-treated cells. However, it inhibited LPS-induced PKB phosphorylation, ratio of ROS and Cu/Zn SOD, and LPS-stimulated AP-1 nuclear translocation.
  
  
  CONCLUSIONS
  We reaffirmed the anti-inflammatory and antioxidant effects of linagliptin. These effects might be related to the three protein kinases. Our findings suggest that linagliptin has a wide range of anti-inflammatory effects.
authors.affiliation: Department of Internal Medicine, Saiyu Soka Hospital, Soka City, Saitama-ken, Japan.; Department of Pharmacology, School of Medicine, Showa University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Chemistry, College of Arts and Sciences, Showa University, Fujiyoshida City, Yamanashi-ken, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Inagaki
authors.affiliation: Department of Pharmacology, School of Medicine, Showa University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tsuji
authors.affiliation: Department of Pharmacology, School of Medicine, Showa University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Gocho
authors.affiliation: Department of Pharmacology, School of Medicine, Showa University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Handa
authors.affiliation: Department of Pharmacology, School of Medicine, Showa University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Hasegawa
authors.affiliation: Department of Toyosu Clinic Preventive Medicine Center, School of Medicine, Showa University, Koto-ku, Tokyo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yura
authors.affiliation: Department of Toyosu Clinic Preventive Medicine Center, School of Medicine, Showa University, Koto-ku, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kawakami
authors.affiliation: Department of Internal Medicine, Saiyu Soka Hospital, Soka City, Saitama-ken, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Ohsawa
authors.affiliation: Department of Internal Medicine, Saiyu Soka Hospital, Soka City, Saitama-ken, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Goto
authors.affiliation: Department of Internal Medicine, Saiyu Soka Hospital, Soka City, Saitama-ken, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Gotoh
authors.affiliation: Department of Pharmacology, School of Medicine, Showa University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kiuchi
keywords: activator protein 1; adenosine 3′,5′-cyclic monophosphate; human umbilical vein endothelial cells; linagliptin; oxidative stress; protein kinase