title: The antidiabetic agent glibenclamide protects airway hyperresponsiveness and inflammation in mice.
abstract: Glibenclamide has a newly discovered role in inflammation regulation besides its antidiabetic effect. As an inhibitor of ATP-sensitive potassium (KATP) channel, glibenclamide antagonizes the relaxation of the tracheal smooth muscle. This indicates that glibenclamide might attenuate airway inflammation while aggravate airway hyperresponsiveness (AHR) in asthmatics. Clinically, many diabetics with asthma are prescribed with glibenclamide to control blood glucose. However, whether glibenclamide could exert any effects on asthmatic inflammation remains unknown. Using an ovalbumin (OVA)-induced mouse model of asthma, we evaluated the effects of glibenclamide on the AHR and inflammation. Interestingly, glibenclamide reduced all the cardinal features of asthma in OVA-challenged mice, including AHR, airway inflammation, and T-helper type 2 (Th2) cytokines. Glibenclamide also downregulated OVA-induced expressions of vascular cell adhesion molecule 1 (VCAM-1) and phosphorylated signal transducer and activator of transcription 6 (p-STAT6) in the lung. In addition, increased sulfonylurea receptor 1 (SUR1) expression in the lung was observed after the OVA challenge. These findings suggest that the classic sulfonylurea glibenclamide plays an important protective role in the development of asthma, which not only provides the evidence for the safety of prescribed glibenclamide in diabetics combined with asthma but also indicates a possible new therapeutic for asthma via targeting glibenclamide-related pathways.
authors.affiliation: Department of Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.forename: Shufang
authors.initials: S
authors.lastname: Zhang
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Cai
authors.forename: Xinlei
authors.initials: X
authors.lastname: Hu
authors.forename: Ruifeng
authors.initials: R
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Chen
authors.forename: Gensheng
authors.initials: G
authors.lastname: Zhang
mesh_terms: D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D002478:Cells, Cultured; D002645:Chickens; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology / Q000633:toxicity; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D016207:Cytokines; D007004:Hypoglycemic Agents; D020011:Protective Agents; D010047:Ovalbumin; D005905:Glyburide
references.citation: J Neurosci. 2003 Sep 17;23(24):8568-77
references.pmid: 13679426
references.citation: Am J Pathol. 2011 Aug;179(2):869-79
references.pmid: 21718679
references.citation: J Cell Biol. 2009 Oct 5;187(1):61-70
references.pmid: 19805629
references.citation: Am J Transplant. 2009 Apr;9(4):687-96
references.pmid: 19292831
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2002 Mar;365(3):220-30
references.pmid: 11882918
references.citation: J Immunol. 2000 Sep 1;165(5):2818-23
references.pmid: 10946314
references.citation: Nat Immunol. 2002 Aug;3(8):715-20
references.pmid: 12145657
references.citation: Immunopharmacol Immunotoxicol. 2001 Aug;23(3):477-86
references.pmid: 11694036
references.citation: Ann Allergy Asthma Immunol. 1998 Jun;80(6):509-16
references.pmid: 9647275
references.citation: J Immunol. 2004 Nov 1;173(9):5766-75
references.pmid: 15494529
references.citation: J Exp Med. 1994 Apr 1;179(4):1145-54
references.pmid: 7511681
references.citation: BMC Complement Altern Med. 2013 Oct 30;13:296
references.pmid: 24171758
references.citation: J Allergy Clin Immunol. 2006 Sep;118(3):551-9; quiz 560-1
references.pmid: 16950269
references.citation: Lipids Health Dis. 2012 Aug 06;11:98
references.pmid: 22867128
references.citation: J Allergy Clin Immunol. 2007 Jun;119(6):1303-10; quiz 1311-2
references.pmid: 17481712
references.citation: Eur Respir J. 1996 Oct;9(10):2057-63
references.pmid: 8902467
references.citation: Am J Pathol. 2013 Apr;182(4):1188-95
references.pmid: 23395089
references.citation: Annu Rev Physiol. 1999;61:337-62
references.pmid: 10099692
references.citation: Nat Med. 2006 Apr;12(4):433-40
references.pmid: 16550187
references.citation: Life Sci. 2011 Nov 7;89(19-20):725-34
references.pmid: 21925514
references.citation: Nat Med. 2002 Aug;8(8):885-9
references.pmid: 12091879
references.citation: Eur J Pharmacol. 2007 Feb 5;556(1-3):215-22
references.pmid: 17182029
references.citation: Am J Physiol Lung Cell Mol Physiol. 2012 Oct 15;303(8):L627-33
references.pmid: 22904168
references.citation: Immunity. 2004 Mar;20(3):267-77
references.pmid: 15030771
references.citation: Arterioscler Thromb Vasc Biol. 1999 Jun;19(6):1421-9
references.pmid: 10364072
references.citation: Allergy. 2013 Mar;68(3):330-8
references.pmid: 23346957
references.citation: J Clin Endocrinol Metab. 2003 Feb;88(2):528-30
references.pmid: 12574174
references.citation: J Pharmacol Exp Ther. 2002 Mar;300(3):946-51
references.pmid: 11861802
references.citation: Clin Infect Dis. 2011 Mar 15;52(6):717-25
references.pmid: 21293047
references.citation: J Cereb Blood Flow Metab. 2009 Feb;29(2):317-30
references.pmid: 18854840
references.citation: Clin Rev Allergy Immunol. 2006 Oct-Dec;31(2-3):107-18
references.pmid: 17085787
references.citation: J Immunol. 1998 Jun 1;160(11):5546-53
references.pmid: 9605159
references.citation: Brain Res. 2011 Apr 18;1385:257-62
references.pmid: 21316351
references.citation: J Clin Invest. 2007 Aug;117(8):2105-13
references.pmid: 17657312
references.citation: Allergy. 2012 Dec;67(12):1547-56
references.pmid: 23057634