Integrin expression by human epidermal keratinocytes can be modulated by interferon-gamma, transforming growth factor-beta, tumor necrosis factor-alpha, and culture on a dermal equivalent.
Receptors of the integrin family are largely confined to the basal layer of keratinocytes, both in human epidermis and in stratified cultures of human keratinocytes. However, suprabasal integrin expression is observed during epidermal wound healing and in psoriatic lesions. We have investigated potential stimuli of suprabasal expression. Addition of transforming growth factor-beta (TGF-beta), interferon-gamma (IFN-gamma), or tumor necrosis factor-alpha (TNF-alpha) to keratinocytes cultured with a 3T3 feeder layer did not induce suprabasal expression. The cytokines caused small changes in the levels of alpha 2 beta 1 or alpha 3 beta 1 on the surface of basal keratinocytes but had no significant effect on the proportion of cells adhering to fibronectin, type IV collagen, and laminin, and did not cause changes in the mobility of integrin subunits on polyacrylamide gels. Injection of TNF-alpha or IFN-gamma intradermally into healthy human volunteers induced an inflammatory response but did not induce suprabasal integrin expression. However, we did observe transient suprabasal integrin expression when keratinocytes were grown on a dermal equivalent consisting of fibroblasts in a collagen gel. One week after raising the cultures to the air-liquid interface, beta 1 integrins were found in all the viable cell layers, with suprabasal cells co-expressing integrins and involucrin; 1 week later integrins were confined to the basal layer. Addition of TGF-beta, IFN-gamma, or TNF-alpha to the dermal equivalents neither induced nor inhibited suprabasal integrin expression. We conclude that suprabasal integrin expression is not induced by the inflammatory cytokines tested, and instead may reflect the proliferation/differentiation status of the epidermis.
Hertle
M D
MD
Keratinocyte Laboratory, Imperial Cancer Research Fund, London, England.
Jones
P H
PH
Groves
R W
RW
Hudson
D L
DL
Watt
F M
FM
D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007231:Infant, Newborn; D016023:Integrins / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology*; D015603:Keratinocytes / Q000737:chemistry*; D008297:Male; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016023:Integrins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma