Production of tumour necrosis factor-α, interleukin-1, interleukin-6 and soluble intercellular adhesion molecule-1 by human keratinocytes stimulated in vitro with gram-negative and gram-positive components

Abstract

Cultured human keratinocytes were analyzed for their ability to release tumour necrosis factor (TNF)-α, interleukin (IL)-1α, IL-6 and soluble intercellular adhesion molecule-1 (sICAM-1) after stimulation with Gram-negative [Salmonella typhimurium porins and lipopolysaccharide (LPS)-R] and Gram-positive components [lipoteichoic acid, muramic acid, muramyl-dipeptide (MDP), adjuvant peptide, protein A, α-haemolysin, toxic shock syndrome toxin (TSST)-1]. The surface expression of ICAM-1 was also investigated. In supernatants of untreated cells, no or minimal amounts of these molecules were found. After stimulation with Salmonella typhimurium porins and LPS-R, significant amounts of TNF-α, IL-1α, IL-6 and sICAM-1 were detected. Protein A induces the release of TNF-α, but not IL-1α, IL-6 and sICAM-1. α-Haemolysin induces IL-1α and IL-6 production. MDP, lipoteichoic acid and TSST-1 were able to induce a significant release of IL-6. TSST-1 also increased the level of sICAM-1 together with adjuvant peptide, which stimulated the production of TNF-α and IL-6. Muramic acid showed an increase of IL-6 release by human keratinocytes. Porins, LPS-R, adjuvant peptide and TSST-1 were also able to upregulate the surface expression of ICAM-1 on keratinocytes. The capacity of these cells to synthesize and release these molecules supports the hypothesis that keratinocytes may play an important role in modulating an immune or inflammatory response