title: Epidermal Dysfunction Leads to an Age-Associated Increase in Levels of Serum Inflammatory Cytokines.
abstract: Even though elderly populations lack visible or other clinical signs of inflammation, their serum cytokine and C-reactive protein levels typically are elevated. However, the origin of age-associated systemic inflammation is unknown. Our previous studies showed that abnormalities in epidermal function provoke cutaneous inflammation, and because intrinsically aged skin displays compromised permeability barrier homeostasis and reduced stratum corneum hydration, we hypothesized here that epidermal dysfunction could contribute to the elevations in serum cytokines in the elderly. Our results show first that acute disruption of the epidermal permeability barrier in young mice leads not only to a rapid increase in cutaneous cytokine mRNA expression but also an increase in serum cytokine levels. Second, cytokine levels in both the skin and serum increase in otherwise normal, aged mice (>12 months). Third, expression of tumor necrosis factor-α and amyloid A mRNA levels increased in the epidermis, but not in the liver, in parallel with a significant elevation in serum levels of cytokines. Fourth, disruption of the permeability barrier induced similar elevations in epidermal and serum cytokine levels in normal and athymic mice, suggesting that T cells play a negligible role in the elevations in cutaneous and serum inflammatory cytokines induced by epidermal dysfunction. Fifth, correction of epidermal function significantly reduced cytokine levels not only in the skin but also in the serum of aged mice. Together, these results indicate that the sustained abnormalities in epidermal function in chronologically aged skin contribute to the elevated serum levels of inflammatory cytokines, potentially predisposing the elderly to the subsequent development or exacerbation of chronic inflammatory disorders.
authors.affiliation: School of Basic Medical Sciences, Tianjin Medical University, Tianjin, People's Republic of China. Electronic address: lizhihuleopard@yahoo.com.
authors.forename: Lizhi
authors.initials: L
authors.lastname: Hu
authors.affiliation: Dermatology Services, Veterans Affair Medical Center and University of California-San Francisco, San Francisco, California, USA.
authors.forename: Theodora M
authors.initials: TM
authors.lastname: Mauro
authors.affiliation: Dermatology Services, Veterans Affair Medical Center and University of California-San Francisco, San Francisco, California, USA; Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Erle
authors.initials: E
authors.lastname: Dang
authors.affiliation: Dermatology Services, Veterans Affair Medical Center and University of California-San Francisco, San Francisco, California, USA.
authors.forename: George
authors.initials: G
authors.lastname: Man
authors.affiliation: School of Basic Medical Sciences, Tianjin Medical University, Tianjin, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Dermatology Services, Veterans Affair Medical Center and University of California-San Francisco, San Francisco, California, USA.
authors.forename: Dale
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Dermatology Services, Veterans Affair Medical Center and University of California-San Francisco, San Francisco, California, USA; Metabolism, Veterans Affair Medical Center and University of California-San Francisco, San Francisco, California, USA.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Feingold
authors.affiliation: Dermatology Services, Veterans Affair Medical Center and University of California-San Francisco, San Francisco, California, USA.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Elias
authors.affiliation: Dermatology Services, Veterans Affair Medical Center and University of California-San Francisco, San Francisco, California, USA. Electronic address: mqman@hotmail.com.
authors.forename: Mao-Qiang
authors.initials: MQ
authors.lastname: Man
mesh_terms: D000375:Aging / Q000502:physiology*; D000682:Amyloid / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D002199:Capillary Permeability / Q000502:physiology*; D016207:Cytokines / Q000097:blood* / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology*; D005990:Glycerol / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D011897:Random Allocation; D018709:Statistics, Nonparametric
chemical_list: D000682:Amyloid; D016207:Cytokines; D005990:Glycerol