title: Impaired cytokine expression, neutrophil infiltration and bacterial clearance in response to urinary tract infection in diabetic mice.
abstract: Diabetic patients have increased susceptibility to infections, and urinary tract infections (UTI) are the most common type in women with diabetes mellitus. Knowledge of bacterial clearance effectiveness following UTI in diabetics is sparse. In this study, the effects of diabetes on bacterial clearance efficiency and components of the innate immune system in response to UTI in a murine model were investigated. Streptozotocin-induced diabetic and control female C57BL/6J mice were infected with uropathogenic Escherichia coli, and bacterial load, expression of chemokines, and neutrophil infiltration in the bladder over time were investigated. Expression levels of histone deacetylases were also measured to address a potential mechanism underlying the phenotype. Bacterial clearance during UTI was significantly prolonged in diabetic mice relative to controls. Neutrophil infiltration in bladder tissue and urine, and both mRNA and protein expression of chemokines MIP-2, KC, MCP-1 and IL-6 in bladder tissue were diminished at early time points after infection in diabetic mice relative to controls. In addition, mRNA levels of histone deacetylases 1-5 were increased in diabetic mice. This is the first study to show an association of impaired bacterial clearance in diabetic mice with suppression of UTI-induced chemokine expression and neutrophil infiltration in the bladder.
authors: Urology Institute, University Hospitals Case Medical Center and Department of Urology, Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, OH 44106, USA Department of Genetics & Genomic Sciences, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
authors: Ahmet
authors: A
authors: Ozer
authors: Urology Institute, University Hospitals Case Medical Center and Department of Urology, Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
authors: Cengiz Z
authors: CZ
authors: Altuntas
authors: Urology Institute, University Hospitals Case Medical Center and Department of Urology, Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, OH 44106, USA Department of Chemistry, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44105, USA.
authors: Fuat
authors: F
authors: Bicer
authors: Urology Institute, University Hospitals Case Medical Center and Department of Urology, Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, OH 44106, USA Department of Chemistry, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44105, USA.
authors: Kenan
authors: K
authors: Izgi
authors: Department of Molecular Microbiology, Center for Women's Infectious Disease Research, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
authors: Scott J
authors: SJ
authors: Hultgren
authors: Urology Institute, University Hospitals Case Medical Center and Department of Urology, Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
authors: Guiming
authors: G
authors: Liu
authors: Urology Institute, University Hospitals Case Medical Center and Department of Urology, Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, OH 44106, USA fxd22@case.edu.
authors: Firouz
authors: F
authors: Daneshgari
mesh_terms: D000818:Animals; D058491:Bacterial Load; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000276:immunology* / Q000382:microbiology; D005260:Female; D020869:Gene Expression Profiling; D006655:Histone Deacetylases / Q000096:biosynthesis / Q000235:genetics; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D001743:Urinary Bladder / Q000473:pathology; D014552:Urinary Tract Infections / Q000276:immunology* / Q000382:microbiology*; D014556:Urine / Q000166:cytology; D056689:Uropathogenic Escherichia coli / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D016207:Cytokines; D006655:Histone Deacetylases
keywords: ELISA; myeloperoxidase; quantitative real-time RT-PCR; type 1 fimbria