Localization of tumour necrosis factor-alpha (TNF-α) and its receptors in normal and psoriatic skin: epidermal cells express the 55-kD but not the 75-kD TNF receptor

Abstract

SUMMARYThe distribution of TNF-a, p55 TNF reeeptor (TNF-R) and p75 TNF-R in normal skin and uninvolved and lesional skin from psoriasis patients has been investigated, using specific mono-and polyclonal antibodies. In normal skin, and uninvolved and lesional skin from psoriasis patients, p55 TNF-R is associated with epidermal keratinocytes and a network of upper dermal dendritic cells. This suggests that the actions oCTNF-a on epidermal ceNs/Hrn-o are mediated by binding to the p55 TNF-R. In Icsionat psoriasis skin, there was staining of the parakeratotic stratum eorneuni and increased expression of p55 TNF-R in association with upper dermal blood vessels. Staining for p75 TNF-R in normal skin was restricted to eccrine sweat ducts and dermal dendritic cells, and was absent from the epidermis. In lesional psoriasis skin, there was slaining for p75 TNF-R in association with upper dermal blood vessels and perivascular infiltrating cells. TNF-a in normal skin was predominantly localized to the basal cell layers ofthe epidermis, and was seen in association with eccrine ducts and sebaceous glands. In lesional psoriasis skin, and to a lesser extent in uninvolved psoriasis skin. TNF-a; was distributed throughout the epidermis, and was also specifically localized to upper dermal blood vessels. Up-regulation of TNF-a. p55 TNF-R and p75 TNF-R on dermal blood vessels in psoriasis may play an important role in the pathogenesis of this condition by promoting cutaneous recruitment of inflatiimatory cells.

Dual Inhibition of TNFR1 and IFNAR1 in Imiquimod-Induced Psoriasiform Skin Inflammation in Mice

“…Although we did not address this issue, we do show that genetic ablation of TNFR1 is sufficient to partially protect mice from the full-blown skin inflammation upon IMQ treatment. Furthermore, we report specific upregulation of TNFR1 in the skin treated with IMQ, drawing another parallel to human psoriasis, in which TNFR1 expression is also increased (43,44). This finding shows another similarity between the IMQ-induced psoriasiform skin inflammation mouse model and human psoriasis.…”

Inflammatory Cytokine Tumor Necrosis Factor-α Enhances Nerve Growth Factor Production in Human Keratinocytes, HaCaT Cells

“…Generally, the response to TNF-α is triggered by binding to one of two distinct receptors, designated TNFR1 (55-kD TNFR) and TNFR2 (75-kD TNFR), which are differentially regulated in various cell types in normal and diseased tissue. In normal and psoriatic skin, epidermal cells express TNFR1 but not TNFR2 (25) and we also confirmed the TNFR1 expression in keratinocytes using quantitative RT-PCR (data not shown), indicating that the TNF-α-enhanced NGF secretion was mediated by TNFR1. However, there was no difference in TNFR1 mRNA expression levels between the TNF-α-treated and -untreated keratinocytes (data not shown).…”

“…TNF-α is a pivotal proinflammatory cytokine of the innate immune response and a key for skin inflammation (23). Plasma TNF-α concentration is increased in atopic dermatitis (24), and TNF-α and its receptors are upregulated in dermal blood vessels from patients with psoriasis (25). IFN-γ is also thought to be one of the important mediators in psoriatic inflammation.…”

Caffeic Acid Reduces Cutaneous Tumor Necrosis Factor Alpha (TNF-α), IL-6 and IL-1β Levels and Ameliorates Skin Edema in Acute and Chronic Model of Cutaneous Inflammation in Mice

“…TNF-α, an autocrine stimulator as well as a potent inducer of other inflammatory cytokines, is produced by keratinocytes, epidermal Langerhans cells (LCs) and macrophages in the papillary dermis, 25) which has been considered a pivotal cytokine and a key mediator in inflammation in the skin. 26,27) In the present paper we further demonstrated that CA markedly inhibited TPA/A23187-induced TNF-α production in human keratinocytes.…”