| Psoriasis is a common, chronic, recurrent, inflammatory disease, it is considered as a multigene-deterrnined hereditary disease now. The pathogenesis of psoriasis involves four types of cells, including keratinocyte (KC), lymphocyte, endothelial cell (EC), and neutrophul. KC and lymphocyte play the most important role in the pathogenesis of psoriasis. Researcheres have spent many years to study the function of KC in psoriatic lesion, and made some progresses, have already proved that expression of cytokines in psoriatic lesion is imbalance. The overexpression of cytokines have been demonstrated and is believed to be of pathogenesis in psoriasis, but its function in the pathogenesis in psoriasis is not yet clear. Under the influence of modem concept of immuno-inflammatory system in psoriasis, the opinion that target of antipsoriatic drugs is cytokine system has been recognized gradually. FK506 is a new immunosuppressive agent,it has been proved in the treatment of psoriasis. But the mechanism of action of FK506 needs further investigate. This aim of the study is to observe nitric oxide (NO),interleukin-lbeta (IL-i 13), interleukin-2 (IL-2),interleukin-8 (IL-8) secretion of IIaCaT cell line TNF- a -induced in vitro effected by FK506 and to further investigate the machanism of cytokine network in psoriatic lesions and the action of FK506 how to have its immunosuppressive effect on KCs in the psoriatic lesions. In the first part of the study, we build the inflammatory model of HaCaT cell line. Firstly, we have carried out the experiment in vitro about suppression of the proliferation of HaCaT cell line TNF- a -induced by different concentrations of FK506 in the different points of time. The static HaCaT cell was stimulated 48hs by different concentrations of FK506, the results indicated that (1) FK506 have theacare suPpression to HaCaT cells When the concelltration of drig above 1 .0 X l0-6M.(2) FK506 have the safe and effective suPPression tO HaCaT cells whe theconcentration of drug betWeen l .0 X l0-6 M and 2.0 X l0-6 M. (3) FK506 hadshown the toxicity of cells. we observed no foedon of cell bulld in the medboWhn the concentration above 2.5 X l0(' M. (4) FK506 shown that there is notsignifican suPPression to the Proliferation of KC When the concedrion of FK506between 1 .0 X l0D M and l l0 X 10-6 M. and secondly according to the data, Whichderive from the eXPerhaent of sUPPrssion of proliferation of HaCaT celI, we btiltthe indaInmatOry model of HaCaT cel1 line TN-F- Q -indued in vitro, Under thecondition of bout the influnce of TNF- Q,we come to the conclusions: (l)It is the eighth hour When FK506 has the most effective influence on HaCaT cellM- Q -induced, and the safe and effective concentration of FK506 is 1.0 X 10-6 M.(2) FK506 has not effected the cytokine secreted by HaCaT cell whout TNF- Q-induced.NO is a relaxing factr derived from EC, meanwhile it is also a imPortanintrasellular and eXtracellular message. Researches have already proved tha NOshows elevated 1evels in psoriatic lesiQn, and is closely associated withinununlogic mechanisms in the pathogenesis ofpsoriasis. In the second part of theStUdy to StUdy NO secretion of HaCaT cell line mF- Q -induced in vitro effected byFK506, to observe wforthout effect, though standard Griess test. To test changesof NO secretion HaCaT cell line in the differen times withjwtthout the action ofFK506. The results indicated tha (l) NO secretion of HaCaT cell line without TNF-Q -indued wer not effected by FK506.(2) NO secretion of HaCaT cell line TNF-Q -induced suPPressed by FK506.(3) FK506 is a effective1y haosuPressiVe andani-inflammatory bog. In the ligh of cytokine netwOrk of immuno-ianaxnmatorypathogene... |
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