| The skin is a frequent site of allergic and inflammatory disorders, which pathogenesis is very complex. Substantial findings show that keratinocytes and dermal fibroblast cells play a crucial role in the allergy, inflammation and immune regulation of skin. They produce various cytokines, such as IL-6, IL-8 , interferon-gamma (IFN-γ) and monocyte chemotatic protein (MCP) with pro- inflammatory function, which can induce inflammatory cells infiltration and lead to the incidence of inflammation.Histamine is an important medium in immediate-type hypersensitivity and related dermatoses, such as urticaria and atopic dermatitis. In addition to its known effects on glands and vessels, recent data have provided further evidence of histamine's pro-inflammatory actions. It plays important roles in cytokine release and in adhesion process. It acts on target cells through distinct histamine receptors (HRs). Most of the effects of histamine in allergic disorders are mediated through H1R. More recently, H1R has been shown to activate the transcription factor NF-κB, which plays a key role in inflammatory gene expression. It implies that H1R can regulate many pro-inflammatory cytokines and chemokines and result in inflammation. Therefore, in order to prevent and treat the allergic inflammation, HRs expression and regulation should be studied.Today antihistamines remain important agents in the treatment of allergic diseases. Recent data show some antihistamines, such as cetirizine, not only alleviate the symptoms of allergic reaction, but also possess anti-inflammatory properties, which can inhibit eosinophil chemotaxis and reduce the IFN-γ-induced expression of adhesion molecule. IFN-γ, which is an essential cytokine released by TH1 cells, plays a key role in T cell-driven inflammation. It stimulates the synthesis of chemokines, induces expression of molecules for the retention activation of T cells. Research on anti-inflammatory mechanism of antihistamines can further demonstrate its action pathway and target.The first aim of this work was to study histamine receptor expression and regulation on both dermal fibroblast cells and keratinocytes. The second was to study the receptor-independent and –dependent anti-inflammatory effects of cetirizine by mimicking the skin inflammatory conditions with histamine and IFN-γ.Results:1 Expression of histamine H1 and H2 receptors in both dermal fibroblast cells and keratinocytes was assessed by flow cytometry. Binding of FITC-labeled histamine was detected in cells. The binding was blocked by unlabeled histamine, H1R and H2R ligands. The cells were blocked about 44% and 69% by histamine, 41% and 59% by mepyramine, 12% and 30% by cimetidine, 31% and 64% by HTMT, 16% and 31% by dimaprit, respectively. The results showed that H1R was expressed in both dermal fibroblast cells and keratinocytes, H2R may be only expressed in keratinocytes.2 Expression of histamine H1 and H2 receptors in both dermal fibroblast cells and keratinocytes was assessed by RT-PCR. The results showed H1R mRNA was only detected in dermal fibroblast cells. While both H1R mRNA and H2R mRNA were expressed in keratinocytes. Furthermore, H1R mRNA was upregulated by histamine in both kinds of cells, significantly upregulated by IFN-γin dermal fibroblast cells, downregulated by TNF-α in two kinds of cells. The result indicated that H1R mRNA was regulated by cytokines and inflammatory mediums.3 Expression of histamine H1 receptor protein in both dermal fibroblast cells and keratinocytes was assessed by means of immunohistochemistry and Western Blot analysis. The results showed H1R protein was expressed in two kinds of cells. After 24 h treatment with 10-5 mol/L histamine and 20 ng/mL IFN-γ, H1R protein level was increased 9% and 47%, while reduced 15.7% by 20 ng/mL TNF-α in dermal fibroblast cells. The tendency in keratinocytes was similar. The results indicated that the regulation of H1R protein level by cytokines may play an important role in allergy and immune inflammation.4 The cell...
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