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.
Perfetto
Brunella
B
Faculty of Medicine and Surgery, Second University of Naples, Department of Sperimental Medicine, Microbiology and Clinical Microbiology, Via Costantinopoli 16, 80138, Naples, Italy
Donnarumma
Giovanna
G
Criscuolo
Daniela
D
Paoletti
Iole
I
Grimaldi
Elena
E
Tufano
Maria Antonietta
MA
Baroni
Adone
A
D000328:Adult; D019898:Autocrine Communication; D002448:Cell Adhesion / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008214:Lymphocytes / Q000166:cytology; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D019899:Paracrine Communication; D010766:Phosphorylation / Q000187:drug effects; D018272:Porins / Q000302:isolation & purification / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000737:chemistry; D012867:Skin / Q000166:cytology; D013205:Staphylococcal Protein A / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000737:chemistry; D013682:Teichoic Acids / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D016207:Cytokines; D020672:I-kappa B Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D018272:Porins; D013205:Staphylococcal Protein A; D013682:Teichoic Acids; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; C009900:lipoteichoic acid