银屑病诱发药物对HaCaT角质形成细胞的影响

为了探讨锂盐、普萘洛尔和氯喹是否通过影响银屑病的细胞因子网络从而诱发或加重银屑病，以不同浓度的碳酸锂、盐酸普萘洛尔或二磷酸氯喹处理HaCaT角质形成细胞后加以TNF-α刺激，应用人类细胞因子抗体分析膜技术测定细胞培养液中多种细胞因子和生长因子的分泌情况；采用实时定量PCR法检测IL-8和IL-6 mRNA的表达。人类细胞因子抗体分析膜技术结果显示，碳酸锂明显促进IL-6和TNF-α的产生；盐酸普萘洛尔明显促进IL-6等多种细胞因子和生长因子的产生；二磷酸氯喹也明显促进IL-6的产生。实时定量PCR结果表明，TNF-α能刺激HaCaT角质形成细胞呈剂量依赖性增加IL-8和IL-6 mRNA的表达(P<0.01)；并对IL-8的调节作用更强(P<0.01)；1×10^-6 mol·L^-1盐酸普萘洛尔能显著上调IL-6 mRNA的表达(P<0.05)。碳酸锂、盐酸普萘洛和二磷酸氯喹对HaCaT角质形成细胞表达以及产生某些细胞因子和生长因子具有调节功能。

Effects of drugs known to trigger psoriasis on HaCaT keratinocytes

To investigate whether lithium carbonate, propranolol or chloroquine aggravate psoriasis through influencing cytokines of the psoriatic cytokine network, HaCaT keratinocytes were stimulated with TNF-a after treatment with these drugs. Protein secretion of a set of multiple different cytokines and growth factors in culture supernatants were measured by using a cytokine antibody array technology. Expression of IL-8 and IL-6 mRNA was determined by real-time PCR. In culture supernatants of TNF-alpha-stimulated HaCaT cells, production of IL-6 and TNF-alpha could be enhanced by lithium carbonate; production of IL-6 and a panel of cytokines and growth factors could be enhanced by propranolol hydrochloride; and IL-6 was up-regulated by chloroquine diphosphate as well. Real-time PCR analysis showed a significantly dose-dependent increase of IL-8 and IL-6 mRNA expression in HaCaT cells stimulated with TNF-a as compared to cells without TNF-alpha-stimulation, the mRNA expression of IL-8 was higher than that of IL-6 with the same concentration of TNF-alpha (P < 0.01). Compared with HaCaT cells cultured with medium alone, propranolol hydrochloride at the concentration of 1 x 10(-6) mol x L(-1) could stimulate HaCaT cells to express higher level of IL-6 mRNA (P < 0.05). The drugs investigated show a modulatory effect on certain cytokines and growth factors which are able to modulate inflammatory type of immune reaction present in psoriatic lesions.