Effects of drugs known to trigger psoriasis on HaCaT keratinocytes / 药学学报

ABSTRACT

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.