Interleukin-6 promotes human epidermal keratinocyte proliferation and keratin cytoskeleton reorganization in culture

Abstract

We have studied the effects of interleukin-6 (IL-6) on human epidermal keratinocytes by using serum-free culture conditions that allow the serial transfer, differentiation, and formation of well-organized multilayered epithelia. IL-6 at 2.5 ng/ml or higher concentrations promoted keratinocyte proliferation, with an ED(50) of about 15 ng/ml and a maximum effect at 50 ng/ml. IL-6 was 10-fold less potent than epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha) and supported keratinocyte growth for up to eight cumulative cell generations. IL-6-treated keratinocytes formed highly stratified colonies with a narrower proliferative/migratory rim than those keratinocytes stimulated with EGF or TGF-alpha; confluent epithelial sheets treated with IL-6 also underwent an increase in the number of cell layers. We also examined the effect of IL-6 on the keratin cytoskeleton. Immunostaining with anti-K16 monoclonal antibodies showed that the keratin network was aggregated and reorganized around cell nucleus and that this was not attributable to changes in keratin levels. This is the first report concerning the induction of the reorganization of keratin intermediate filaments by IL-6 in human epidermal keratinocytes.

Dopamine Agonists Upregulate IL-6 and IL-8 Production in Human Keratinocytes

“…It is known that IL-6 and IL-8 stimulate the proliferation of human keratinocytes and their overexpression is related to inflammatory and hyperproliferative disorders of the skin [9,11,12,41] . Furthermore, dopaminergic and adrenergic receptors are known to be involved in the skin healing processes [17,42] .…”

“…volved in the proliferation and differentiation of epidermal cells [9] . Modifications in the regulatory pathways of IL-6 are related to abnormal inflammatory and proliferative processes, such as keloid formation during the wound healing process [10] .…”

Inflammatory mediators in gastroesophageal reflux disease: impact on esophageal motility, fibrosis, and carcinogenesis

“…Acid-induced H 2 O 2 contributes to increased proliferation and decreased apoptosis in esophageal adenocarcinoma cells (38). In addition, other inflammatory mediators, such as IL-1, IL-6, or IL-8, are known to enhance epithelial turnover (47,123,139).…”

Comano's (Trentino) thermal water interferes with interleukin-6 production and secretion and with cytokeratin-16 expression by cultured human psoriatic keratinocytes: Further potential mechanisms of its anti-psoriatic action

“…All haemopoietins share the gp130 signal-transducing subunit (21). IL-6 acts as a growth factor for keratinocytes either directly via its specific receptor signalling (22)(23)(24) and/or indirectly by inducing the production and release of keratinocyte growth factor (KGF) by dermal fibroblasts (25). Non-activated normal keratinocytes express low levels of IL-6-specific mRNA and release only tiny amounts of IL-6 (26).…”