9th International BAU Drug Design Congress, İstanbul, Türkiye, 29 Kasım - 02 Aralık 2023
Introduction: Psoriasis is a lifelong inflammatory skin disease. Since cytokines (IL-1β, IL-6) are important in its pathophysiology, agents that reduce the cytokines is a logical approach for the development of new therapeutics. Trimetazidine (TMZ), an antianginal drug with a favorable safety profile, demonstrates antiinflammatory properties by reducing IL-1β activity in experimental studies, however it has not been examined in an inflammatory skin disease model. This study aims to investigate the antiinflammatory and antiproliferative effects of TMZ on HaCaT cells, a keratinocyte cell line from adult human skin.
Method: HaCaT cells were incubated with lipopolysaccharide (LPS; 1 µg/ml for 24 hours) to induce in vitro psoriasis. During LPS incubation, cells were treated with TMZ (25-50-75-100 µM) or vehicle (DMEM, as control). Cell proliferation and IL-1β were measured with WST-1 colorimetric assay and commercially available ELISA, respectively.
Results: TMZ (50, 75,100 µM) concentration-dependently inhibited LPS-induced proliferation of HaCaT cells (p<0.001). At 75 and 100 µM concentrations, TMZ also decreased viability of non-LPS treated cells (p<0.05). IL-1β did not change in cells treated with both LPS and TMZ. In contrast, 50 and 75 µM of TMZ increased IL-1β (p<0.05) in non-LPS treated cells.
Conclusion: TMZ demonstrated a strong antiproliferative effect in LPS- treated HaCaT cells with an unexpected change in IL-1β in non-LPS treated cells. Potential of TMZ as an antipsoriatic agent and mechanism of action on cytokines requires further studies. This study was supported by the TUBITAK 2209A Support Program (Project no 1919B012112223 to BD).
Key words: psoriasis, HaCaT, trimetazidine, inflammation