skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Leptin deficiency-induced obesity exacerbates ultraviolet B radiation-induced cyclooxygenase-2 expression and cell survival signals in ultraviolet B-irradiated mouse skin

Abstract

Obesity has been implicated in several inflammatory diseases and in different types of cancer. Chronic inflammation induced by exposure to ultraviolet (UV) radiation has been implicated in various skin diseases, including melanoma and nonmelanoma skin cancers. As the relationship between obesity and susceptibility to UV radiation-caused inflammation is not clearly understood, we assessed the role of obesity on UVB-induced inflammation, and mediators of this inflammatory response, using the genetically obese (leptin-deficient) mouse model. Leptin-deficient obese (ob/ob) mice and wild-type counterparts (C57/BL6 mice) were exposed to UVB radiation (120 mJ/cm{sup 2}) on alternate days for 1 month. The mice were then euthanized and skin samples collected for analysis of biomarkers of inflammatory responses using immunohistochemistry, western blotting, ELISA and real-time PCR. Here, we report that the levels of inflammatory responses were higher in the UVB-exposed skin of the ob/ob obese mice than those in the UVB-exposed skin of the wild-type non-obese mice. The levels of UVB-induced cyclooxygenase-2 expression, prostaglandin-E{sub 2} production, proinflammatory cytokines (i.e., tumor necrosis factor-alpha, interleukin-1beta, interleukin-6), and proliferating cell nuclear antigen and cell survival signals (phosphatidylinositol-3-kinase and p-Akt-Ser{sup 473}) were higher in the skin of the ob/ob obese mice than the those in skin of their wild-type non-obesemore » counterparts. Compared with the wild-type non-obese mice, the leptin-deficient obese mice also exhibited greater activation of NF-kappaB/p65 and fewer apoptotic cells in the UVB-irradiated skin. Our study suggests for the first time that obesity in mice is associated with greater susceptibility to UVB-induced inflammatory responses and, therefore, obesity may increase susceptibility to UVB-induced inflammation-associated skin diseases, including the risk of skin cancer.« less

Authors:
 [1];  [2];  [3];  [3];  [3]
  1. Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States)
  2. Birmingham Veterans Administration Medical Center, Birmingham, AL 35294 (United States)
  3. (United States)
Publication Date:
OSTI Identifier:
21344935
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 244; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2010.01.010; PII: S0041-008X(10)00021-9; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIGENS; BIOLOGICAL MARKERS; ENZYME IMMUNOASSAY; HAZARDS; INFLAMMATION; LEPTIN; LYMPHOKINES; MELANOMAS; METABOLIC DISEASES; MICE; PROSTAGLANDINS; SKIN; SKIN DISEASES; ULTRAVIOLET RADIATION; ANIMALS; BIOASSAY; BODY; CARCINOMAS; DISEASES; ELECTROMAGNETIC RADIATION; EPITHELIOMAS; GROWTH FACTORS; HORMONES; IMMUNOASSAY; MAMMALS; MITOGENS; NEOPLASMS; ORGANIC COMPOUNDS; ORGANS; PATHOLOGICAL CHANGES; PEPTIDE HORMONES; PEPTIDES; POLYPEPTIDES; PROTEINS; RADIATIONS; RODENTS; SYMPTOMS; VERTEBRATES

Citation Formats

Sharma, Som D., Katiyar, Santosh K., E-mail: skatiyar@uab.ed, Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, Clinical Nutrition Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294. Leptin deficiency-induced obesity exacerbates ultraviolet B radiation-induced cyclooxygenase-2 expression and cell survival signals in ultraviolet B-irradiated mouse skin. United States: N. p., 2010. Web. doi:10.1016/j.taap.2010.01.010.
Sharma, Som D., Katiyar, Santosh K., E-mail: skatiyar@uab.ed, Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, Clinical Nutrition Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, & Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294. Leptin deficiency-induced obesity exacerbates ultraviolet B radiation-induced cyclooxygenase-2 expression and cell survival signals in ultraviolet B-irradiated mouse skin. United States. doi:10.1016/j.taap.2010.01.010.
Sharma, Som D., Katiyar, Santosh K., E-mail: skatiyar@uab.ed, Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, Clinical Nutrition Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294. Sat . "Leptin deficiency-induced obesity exacerbates ultraviolet B radiation-induced cyclooxygenase-2 expression and cell survival signals in ultraviolet B-irradiated mouse skin". United States. doi:10.1016/j.taap.2010.01.010.
@article{osti_21344935,
title = {Leptin deficiency-induced obesity exacerbates ultraviolet B radiation-induced cyclooxygenase-2 expression and cell survival signals in ultraviolet B-irradiated mouse skin},
author = {Sharma, Som D. and Katiyar, Santosh K., E-mail: skatiyar@uab.ed and Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294 and Clinical Nutrition Research Center, University of Alabama at Birmingham, Birmingham, AL 35294 and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294},
abstractNote = {Obesity has been implicated in several inflammatory diseases and in different types of cancer. Chronic inflammation induced by exposure to ultraviolet (UV) radiation has been implicated in various skin diseases, including melanoma and nonmelanoma skin cancers. As the relationship between obesity and susceptibility to UV radiation-caused inflammation is not clearly understood, we assessed the role of obesity on UVB-induced inflammation, and mediators of this inflammatory response, using the genetically obese (leptin-deficient) mouse model. Leptin-deficient obese (ob/ob) mice and wild-type counterparts (C57/BL6 mice) were exposed to UVB radiation (120 mJ/cm{sup 2}) on alternate days for 1 month. The mice were then euthanized and skin samples collected for analysis of biomarkers of inflammatory responses using immunohistochemistry, western blotting, ELISA and real-time PCR. Here, we report that the levels of inflammatory responses were higher in the UVB-exposed skin of the ob/ob obese mice than those in the UVB-exposed skin of the wild-type non-obese mice. The levels of UVB-induced cyclooxygenase-2 expression, prostaglandin-E{sub 2} production, proinflammatory cytokines (i.e., tumor necrosis factor-alpha, interleukin-1beta, interleukin-6), and proliferating cell nuclear antigen and cell survival signals (phosphatidylinositol-3-kinase and p-Akt-Ser{sup 473}) were higher in the skin of the ob/ob obese mice than the those in skin of their wild-type non-obese counterparts. Compared with the wild-type non-obese mice, the leptin-deficient obese mice also exhibited greater activation of NF-kappaB/p65 and fewer apoptotic cells in the UVB-irradiated skin. Our study suggests for the first time that obesity in mice is associated with greater susceptibility to UVB-induced inflammatory responses and, therefore, obesity may increase susceptibility to UVB-induced inflammation-associated skin diseases, including the risk of skin cancer.},
doi = {10.1016/j.taap.2010.01.010},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 244,
place = {United States},
year = {2010},
month = {5}
}