TNF-a, IL-1a, IL-6 and ICAM-1 Expression in Human Keratinocytes Stimulated in Vitro with Escherichia Coli Heat-Shock Proteins

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Abstract
Bacterial heat-shock proteins (HSPs) from Escherichia coli (GroES, GroEL and DnaK) were studied for their ability to induce by themselves the expression and release of tumour necrosis factor-α (TNF-α), interleukin-6 (IL-1α), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) by cultured human keratinocytes. The surface expression of ICAM-1 was also investigated. In the supernatants of untreated cells none or a minimal amount of these molecules was found. After 48 h of stimulation with GroEL significant amounts of TNF-α, IL-1α, IL-6 and soluble ICAM-1 were detected, reaching maximum concentrations at 1 μg ml-1. The same effect was elicited by DnaK but to a lesser extent. Treatment of keratinocytes with GroEL and DnaK also increased TNF-α, IL-1α, IL-6 and ICAM-1 mRNA levels. GroES showed significant activity only on the expression and release of IL-6. GroEL and DnaK were also able to up-regulate the surface expression of ICAM-1 on keratinocytes. The effects on ICAM-1 expression seemed to be directly due to HSPs and not mediated via cytokines. Furthermore, these effects were due to the properties of HSPs because they were inhibited by specific monoclonal antibodies. These findings support the potential role of HSPs in modulating cell interactions during immunological and inflammatory responses in the skin.