title: Altered gene expression profiles associated with enhanced skin inflammation induced by 12-O-tetradecanoylphorbol-13-acetate in streptozotocin-diabetic mice.
abstract: To examine the mechanisms of diabetes-enhanced inflammation, ear inflammation was induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in streptozotocin (STZ)-injected diabetic and control mice. The inflammatory response was determined from ear thickness and histology. The mRNA expression of several inflammation-related genes 8, 24 and 32 h after TPA treatment was determined by quantitative real-time RT-PCR. Ear thickness did not differ between the two groups at 8 h, but was greater in the diabetic mice than control mice at 24 and 32 h (late phase). STZ-diabetic conditions variously affected TPA-induced gene expression. The changes 8 h after TPA treatment probably reflected transcriptional regulation, and the genes were divided into three groups, up-regulated (IL-6, MCP-1, HO-1 and SOCS3), unregulated (IL-1beta, TNF-alpha and IL-10) and down-regulated (RANTES) genes. TPA-induced gene expression of cytokines, except for RANTES, peaked at 8 h and significantly declined in the late phase in control mice, while the expression of IL-1beta and TNF-alpha did not decline in the late phase in the diabetic mice. This result indicated the destabilization process for these mRNA, a type of post-transcriptional regulation, to be impaired under STZ-induced diabetic conditions; however, TPA-induced gene and protein expression of TTP, an RNA-binding protein involved in mRNA decay, were adversely enhanced in the diabetic mice. These findings suggested that STZ-induced diabetes affected the transcriptional and post-transcriptional control of TPA-induced inflammation, and greater mRNA levels of IL-1beta and TNF-alpha in the late phase were probably responsible for the diabetes-enhanced inflammation.
authors: Department of Life Science, Faculty of Science and Engineering, Setsunan University, Neyagawa, Osaka 572-8508, Japan. iba@lif.setsunan.ac.jp
authors: Yoshinori
authors: Y
authors: Iba
authors: Koushi
authors: K
authors: Watanabe
authors: Kiyokazu
authors: K
authors: Ozaki
authors: Osamu
authors: O
authors: Aozasa
authors: Keisuke
authors: K
authors: Ishizawa
authors: Tetsuro
authors: T
authors: Matsuura
authors: Hiroshi
authors: H
authors: Oyama
authors: Tohru
authors: T
authors: Masukawa
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003872:Dermatitis / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000276:immunology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011499:Protein Processing, Post-Translational; D012867:Skin / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D015533:Transcriptional Activation
chemical_list: C554292:12-O-tetradecanoylphorbol-1,3-acetate; D016207:Cytokines; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013755:Tetradecanoylphorbol Acetate