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

Publisher Website
Google Scholar
Abstract
Tumor necrosis factor α (TNF‐α) is a pleiotropic proinflammatory cytokine that elicits a large number of biological effects, including inflammatory and immuno‐regulatory responses. Biological activities of TNF‐α are mediated by two distinct TNF receptors, p55 type 1 receptor (TNFR1) and p75 type 2 receptor (TNFR2). To determine the role of TNF‐α 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‐α (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‐α (20–200 ng for 3 days), while they showed minimal reactivity to low doses of TNF‐α (0.2–2 ng for 3 days). TNF‐α 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‐α, while keratinocytes from TNFR1(−) mice did not show any up‐regulation of IL‐6. TNF‐α 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‐α.