title: High-Glucose Environment Inhibits p38MAPK Signaling and Reduces Human β-Defensin-3 Expression [corrected] in Keratinocytes.
abstract: Diabetes mellitus is characterized by elevated plasma glucose and increased rates of skin infections. Altered immune responses have been suggested to contribute to this prevalent complication, which involves microbial invasion. In this study we explored the effects of a high-glucose environment on the innate immunity of keratinocytes by focusing on β defensin-3 (BD3) using in vivo and in vitro models. Our results demonstrated that the perilesional skins of diabetic rats failed to show enhanced BD3 expression after wounding. In addition, high-glucose treatment reduced human BD3 (hBD3) expression of cultured human keratinocytes. This pathogenic process involved inhibition of p38MAPK signaling, an event that resulted from increased formation of advanced glycation end products. On the other hand, toll-like receptor-2 expression and function of cultured keratinocytes were not significantly affected by high-glucose treatment. In summary, high-glucose conditions inhibited the BD3 expression of epidermal keratinocytes, which in turn contributed to the frequent occurrences of infection associated with diabetic wounding.
authors: Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors: Cheng-Che E
authors: CC
authors: Lan
authors: Ching-Shuang
authors: CS
authors: Wu
authors: Shu-Mei
authors: SM
authors: Huang
authors: Hsuan-Yu
authors: HY
authors: Kuo
authors: I-Hui
authors: IH
authors: Wu
authors: Chien-Hui
authors: CH
authors: Wen
authors: Chee-Yin
authors: CY
authors: Chai
authors: Ai-Hui
authors: AH
authors: Fang
authors: Gwo-Shing
authors: GS
authors: Chen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000235:genetics*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D034622:RNA Interference; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism / Q000503:physiopathology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology; D023083:beta-Defensins / Q000235:genetics* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C422950:DEFB103A protein, human; D007093:Imidazoles; D011725:Pyridines; D051195:Toll-Like Receptor 2; D023083:beta-Defensins; C560914:beta-defensin 3, rat; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; C093642:SB 203580