Tumor necrosis factor (TNF) receptor type 1 (p55) is a main mediator for TNF-alpha-induced skin inflammation.
Tumor necrosis factor alpha (TNF-alpha) is a pleiotropic proinflammatory cytokine that elicits a large number of biological effects, including inflammatory and immunoregulatory responses. Biological activities of TNF-alpha are mediated by two distinct TNF receptors, p55 type 1 receptor (TNFR1) and p75 type 2 receptor (TNFR2). To determine the role of TNF-alpha in the induction of inflammatory responses in the skin, gene-targeted mutant mice lacking either TNFR1 or TNFR2 were painted with irritant chemicals. Both phenol and croton oil painting onto the ears induced less inflammation in TNFR1(-) mice than normal and TNFR2(-) mice. Intradermal injection of TNF-alpha (0.2-200 ng for 3 days) into the ear induced less inflammation in TNFR1(-) mice than in normal mice. TNFR2(-) mice developed a normal inflammatory reaction to high doses of TNF-alpha (20-200 ng for 3 days), while they showed minimal reactivity to low doses of TNF-alpha (0.2-2 ng for 3 days). TNF-alpha is known to trigger the release of a series of other cytokines and to induce the expression of cell adhesion molecules, thus contributing to the development of inflammation. The levels of protein and mRNA for interleukin (IL)-6 were elevated in keratinocytes from normal as well as TNFR2(-) mice after treatment with TNF-alpha, while keratinocytes from TNFR1(-) mice did not show any up-regulation of IL-6. TNF-alpha induced intercellular adhesion molecule (ICAM)-1 expression in the keratinocytes from normal and TNFR2(-) mice, but not in those from TNFR1(-) mice. These results indicate that TNFR1 is critical for induction of skin inflammation by TNF-alpha.
Kondo
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Division of Dermatology, Sunnybrook Health Science Centre, University of Toronto, Ontario, Canada. seiji@sapmed.ac.jp
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D000287:Administration, Topical; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D007271:Injections, Intradermal; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007509:Irritants / Q000633:toxicity; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012867:Skin / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000378:metabolism*
D015703:Antigens, CD; D016207:Cytokines; D007509:Irritants; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1