title: Cutaneous barrier repair and pathophysiology following barrier disruption in IL-1 and TNF type I receptor deficient mice.
abstract: Disruption of the permeability barrier elicits a homeostatic repair response which rapidly restores barrier function while repeated barrier perturbation results in cutaneous pathology. In response to barrier disruption there is a marked increase in epidermal TNF-alpha and IL-1 production. To determine the potential role of TNF and IL-1 in mediating the cutaneous changes that occur following barrier disruption we compared the kinetics of barrier recovery and the degree of epidermal hyperplasia and cutaneous inflammation in TNF type I (p55) receptor and IL-1 receptor type I (p80) deficient mice. No abnormalities in epidermal morphology were observed with light or electron microscopy in receptor deficient mice. Under baseline conditions epidermal barrier function was unchanged in receptor deficient mice. Following barrier disruption the kinetics of barrier recovery were similar in control vs TNF receptor deficient mice regardless if the barrier was disrupted by acetone treatment, SDS treatment, or tape stripping. In contrast, barrier recovery was slightly but significantly accelerated regardless of the method of barrier disruption in IL-1 receptor deficient mice. The degree of epidermal hyperplasia and cutaneous inflammation following repeated barrier disruption was similar in control, TNF receptor, and IL-1 receptor deficient mice. The present study demonstrates that barrier recovery is not delayed and the degree of epidermal hyperplasia and inflammation are not altered in either TNF receptor or IL-1 receptor deficient mice, indicating that neither TNF nor IL-1 alone are essential for either barrier repair or the cutaneous pathology induced by barrier perturbation. Whereas the increase in IL-1 following barrier disruption may delay components of the repair response, whether either TNF-alpha or IL-1 regulate aspects of the homeostatic response remains unresolved.
authors.affiliation: Department of Medicine, University of California, San Francisco, USA.
authors.forename: M Q
authors.initials: MQ
authors.lastname: Man
authors.forename: L
authors.initials: L
authors.lastname: Wood
authors.forename: P M
authors.initials: PM
authors.lastname: Elias
authors.forename: K R
authors.initials: KR
authors.lastname: Feingold
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D003872:Dermatitis / Q000209:etiology / Q000473:pathology; D004817:Epidermis / Q000473:pathology; D006965:Hyperplasia / Q000473:pathology; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D010539:Permeability; D017472:Receptors, Interleukin-1 / Q000172:deficiency* / Q000235:genetics; D053573:Receptors, Interleukin-1 Type I; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D012016:Reference Values; D012867:Skin / Q000378:metabolism / Q000503:physiopathology* / Q000648:ultrastructure
chemical_list: D015703:Antigens, CD; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I