Keratinocyte growth regulation by the products of immune cells.

Abstract

The induction of a delayed-type cell-mediated immune response in the skin of leprosy patients leads to extensive mononuclear cell accumulation in the dermis and alterations in the keratinocytes of the overlying epidermis (1) . This includes keratinocyte proliferation, epidermal thickening, the expression of IFN-y-induced peptide, IP-10 (2), and surface Ia antigen (1) . Intradermal injection of human rIFN-y into the skin of leprosy patients mimics the delayed cellular response to soluble antigen (3, 4) . Not only are mononuclear leukocytes recruited into the dermal site, but proliferation and antigenic changes of the epidermal keratinocytes are also observed. In an effort to better understand the intercellular dialogues that occur in a cutaneous cell-mediated immune response, we have developed an in vitro assay to detect changes in keratinocyte multiplication in response to inflammatory cell supernatants and purified or recombinant cytokines . Evidence is presented that activated PBMC produce factors that modify keratinocyte growth and differentiation . Our results suggest that T lymphocytes are the cells responsible for this activity. We show that IFNy and transforming growth factor ß (TGF ß)t inhibit keratinocyte growth, whereas IL-3 and granulocyte/monocyte colony-stimulating factor (GM-CSF) stimulate keratinocyte growth.

Identification of macrophage migration inhibitory factor (MIF) in human skin and its immunohistochemical localization

“…Recently, Wistow et al reported that MIF mRNA expression was correlated with cell differentiation of lens cells [18]. This finding suggests the possibility that MIF produced during the immune reaction and inflammatory processes may cause epidermal hyperplasia since skin epidermal hyperplasia and inflammation are considered to be linked to bioactions of localized cytokines and growth factors [14]. This possibility is supported by the fact that the basal cells of the epidermis are highly proliferative in nature.…”

“…For example, IL-1 and TNF-ct release from keratinocytes are induced by ultraviolet radiation [11,12], and physical damage to keratinocytes can stimulate IL-1 release [13]. In addition, IL-1 in concert with other cytokines such as GM-CSF, IL-6, and TGF-t~, stimulates keratinocyte proliferation [14,15]. That is, it is very likely that cytokines are a vital element of the pathological mechanism in inflammatory skin diseases.…”

Prophylaxis and treatment of chemo- and radiotherapy-induced oral mucositis – are there new strategies?

“…[113][114][115][116][117] The action of G-/GM-CSF was thought to be initially restricted to haematopoiesis alone. Laboratory studies have shown however, that G-/GM-CSF influence proliferation and migration of non-haematopoietic cells, including endothelial cells 118 and keratinocytes, 119 suggesting that they may act as regulatory signals outside the haematopoietic system. Clinical studies using subcutaneous G-CSF or GM-CSF have shown a beneficial effect on oral mucositis 110,[120][121][122][123][124][125][126] (Table 3).…”

Cutaneous barrier perturbation stimulates cytokine production in the epidermis of mice.

“…Finally, numerous in vitro studies have shown that cytokines regulate a wide array ofcellular processes in keratinocytes ( 15). For example, both the growth and differentiation of cultured keratinocytes are profoundly altered by the addition of selected cytokines (23)(24)(25). Because The mTNF alpha cDNA probe (B9) was obtained from Dr. Bruce Beutler (University of Texas, Southwestern Medical School, Dallas, TX).…”