Bacterial components induce cytokine and intercellular adhesion molecules-1 and activate transcription factors in dermal fibroblasts

This study investigated the effect of various structural components of Gram-positive (lipotheichoic acid and protein A) and Gram-negative (porins and lipopolysaccharide) bacteria on human dermal fibroblasts. Fibroblasts are important effector cells which have a potential role in augmenting the inflammatory response in various diseases. In this study we present a profile of TNF-alpha, IL-6 and IL-8, the expression of intercellular adhesion molecules (ICAM-1) and the activation of transcriptional nuclear factor NF-kB and AP-1 in human dermal fibroblasts stimulated by bacterial surface components. Compared to the controls, increased ICAM-1, IL-6 and IL-8 gene expression after stimulation of LPS and porins at 2 and 4 h was more evident than that obtained following stimulation of LTA and PA. Gene expression was also associated with the production of cytokine proteins in culture supernatants. TNF-alpha gene expression remained undetectable. Moreover, LPS and porin treatments determined IkBalpha phosphorylation and degradation in human dermal fibroblasts and the subsequent activation of nuclear factors NF-kB and AP-1. These data suggest the importance of such stimuli in the first step of the inflammatory process, as well as the important role played by fibroblasts in skin inflammatory disease.