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

Journal Article · Sat May 01 00:00:00 EDT 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2010.01.010· OSTI ID:21344935

Sharma, Som D ^[1]

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1. Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States)

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.

• OSTI ID: 21344935
• Journal Information: Toxicology and Applied Pharmacology, Vol. 244, 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.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

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