Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibroblasts from different regions of the human body exhibit substantial phenotypic diversity, some of which relates to the capacity for cross-talk with cells of the immune system. We examine, for the first time, thyroid fibroblast biology in culture. Thyroid explants were placed in culture, and fibroblasts were outgrown and serially passaged. These fibroblasts take on a morphology in culture resembling cells from other anatomic regions. When treated with PGE2, they assume a stellate morphology similar to that of prostanoid-treated orbital fibroblasts. The ganglioside profile exhibited by these cells is distinct from that observed previously in orbital and dermal fibroblasts. They uniformly express Thy-1, a surface glycoprotein. Messenger RNA encoding CD40, a surface receptor found on bone marrow-derived cells, and CD40 protein were expressed constitutively at low levels. Interferon-gamma (500 U/ml) treatment for 48-72 h resulted in high levels of surface HLA-DR and CD40 display. When CD40 is engaged with CD40 ligand (CD40L), nuclear factor-kappaB binding activity is up-regulated as is interleukin (IL)-6 and IL-8 expression. IL-1beta treatment up-regulates the expression of IL-1alpha, IL-1beta, and PGE2. These observations suggest that thyroid fibroblasts possess the molecular machinery necessary for cross-talk with immunocompetent cells such as lymphocytes and mast cells through the CD40/CD40L complex, as well as through classic cytokine networks, and to participate potentially in the inflammatory response of the thyroid gland.
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PMID:Human thyroid fibroblasts exhibit a distinctive phenotype in culture: characteristic ganglioside profile and functional CD40 expression. 938 46

Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology that is characterized by tissue fibrosis, which may result from the activation of lesional fibroblasts exhibiting excessive production of extracellular matrix components. However, it has yet to be determined how SSc fibroblasts are activated. CD40 is a cell surface molecule expressed on various cells that is important for the response to activated T cells through CD154. CD40 mRNA was found to be constitutively expressed in both SSc and normal fibroblasts by reverse transcription PCR. Expression of CD40 protein was increased on SSc fibroblasts compared to normal fibroblasts as measured by flow cytometry. Ligation of CD40 by recombinant human CD154 (0.5-2 microg/ml) resulted in increased production of IL-6, IL-8, and monocyte chemoattractant protein-1 in SSc fibroblasts in a dose-dependent manner, whereas these phenomena were not shown in normal fibroblasts even with the addition of CD154. CD80, a costimulatory molecule, was also induced on SSc fibroblasts by CD40 ligation. In the present study, our findings suggest the possibility of a cell-mediated response between fibroblasts and T cells in the lesional skin of SSc patients. Since it is suggested that the CD40-CD154 system may play a crucial role in the aberrant production of immune mediators by SSc fibroblasts, blockage of CD40-CD154 may be a novel therapeutic strategy for SSc.
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PMID:Increased CD40 expression in skin fibroblasts from patients with systemic sclerosis (SSc): role of CD40-CD154 in the phenotype of SSc fibroblasts. 1451 63