| Backgrand and Aims Allergic diseases are common in department of dermatology, and investigation of the mechanisms and development of new effective therapies are very important. It's well proved that histamine and arachidonic acid are crucial mediators in this field. Research showed that nuclear factor-κB(NF-κB) would be activated after histamine bind to its specific H1 receptor, and then activated NF-κB promoted the mRNA expression of many kinds of inflammation mediators. These events produced abundance inflammation mediator proteins, which participated in and aggravated the inflammation. The anti-histamines can antagonise this phenomenon. In present study,we cultivated nasal polyps and skin tissue in vitro and added histamine and arachidonic acid to observe whether they can induce the allergic inflammation. Several anti-histamines were added to detect if they can inhibit the inflammation.Materials and Methods The nasal polyps or skin tissue were cultivated with mizolastine, cetirzine, loratadine, fexofenadine, dexamethasone, and ciclosporin A separately, and then histamine and arachidonic acid were added. Twenty-four hours later the total RNA of polyps or skin tissue was obtained and purified with Tripure isolation reagent. The mRNA expression levels of monocyte chemotactic protein-1(MCP-1),monocyte chemotactic protein-3(MCP-3),regulated upon activation, normal T cell expressed and secreted(RANTES),eotaxin were analyzed by RT-PCR methods. The concentrations of interleukin-4 (IL-4),interleukin-5 (IL-5) and tumor necrosis factor-α(TNF-α) in cultivated supernatant were detected by ELISA methods. Furthermore,the nasal polyps were cultivated with different concentration of mizolastine, and then histamine and arachidonic acid were added. We detect the MCP-1,MCP-3,RANTES and eotaxin by RT-PCR methods and the concentrations of IL-4,IL-5 and TNF-α in cultivated supernatant were detected by ELISA methods.Results We cultivated the nasal polyps and skin tissue in vitro successfully,and then we distilled the RNA and detected the target gene expression by RT-PCR. Cytokines in cultivated supernatant were detected by ELISA methods. In mizolastine group of cultivated nasal polyps, the MCP-1 mRNA expression was significantly weaker than those in both loratadine and fexofenadine groups; the MCP-3 mRNA expression was significantly weaker than those in both cetirzine and loratadine groups; the RANTES mRNA expression was significantly weaker than those in both loratadine and fexofenadine groups; the eotaxin mRNA expression was significantly weaker compare with that in cetirzine group(P<0.05). The levels of IL-4 and IL-5 in supernatant in mizolastine group were significantly lower than those in both cetirzine and loratadine groups, while the levels of TNF-α had no significant difference among all the groups. The MCP-1 mRNA expression in the mizolastine group of cultivated skin tissue was significantly weaker than those in cetirzine,loratadine and fexofenadine groups; the MCP-3 mRNA expression was significantly weaker than those in both cetirzine and loratadine groups; the RANTES mRNA expression was significantly weaker than those in loratadine group; the eotaxin mRNA expression was significantly weaker compare with that in loratadine group(P<0.05). The levels of IL-4 in supernatant in mizolastine group was significantly lower than those in fexofenadine group, and the levels of IL-5 was significantly lower than those in cetirzine,loratadine and fexofenadine groups, while the levels of TNF-α was significantly lower than those in loratadine group.There is significant difference between different concentrations of mizolastine to inhibit the expression of all the detected chemokines and cytokines.Conclusion Histamine and arachidonic acid can induce the tissue to express the chemokines mRNA(MCP-1,MCP-3,RANTES and eotaxin)and cytokines(IL-4,IL-5 and TNF-α)excessively.Compared with other anti-histamines, mizolastine can inhibit the expression of chemokines and cytokines more strongly than those of cetirzine,lora... |
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