Tumor necrosis factor (TNF) receptor type 1 (p55) is a main mediator for TNF-alpha-induced skin inflammation

Eur J Immunol. 1997 Jul;27(7):1713-8. doi: 10.1002/eji.1830270718.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / physiology*
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Inflammation / chemically induced
  • Inflammation / immunology
  • Inflammation / pathology
  • Injections, Intradermal
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Irritants / toxicity
  • Keratinocytes / immunology
  • Keratinocytes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / physiology*
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Skin / pathology*
  • Tumor Necrosis Factor-alpha / administration & dosage
  • Tumor Necrosis Factor-alpha / metabolism*


  • Antigens, CD
  • Cytokines
  • Irritants
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1