Cytomodulatory characteristics of Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) against cypermethrin on skin fibroblast cells (HFF-1)

Abstract

The hematopoietic factor granulocyte macrophage-colony stimulating factor (GM-CSF) has been identified via its capacity to promote bone marrow progenitors' development and differentiation into granulocytes and macrophages. Extensive pre-clinical research has established its promise as a critical therapeutic target in an assortment of inflammatory and autoimmune disorders. Despite the broad literature on GM-CSF as hematopoietic of stem cells, the cyto/geno protective aspects remain unknown. This study aimed to assess the cyto/geno protective possessions of GM-CSF on cypermethrin-induced cellular toxicity on HFF-1 cells as an in vitro model. In pre-treatment culture, cells were exposed to various GM-CSF concentrations (5, 10, 20, and 40 ng/mL) with cypermethrin at IC50 (5.13 ng/mL). Cytotoxicity, apoptotic rates, and genotoxicity were measured using the MTT, Annexin V-FITC/PI staining via flow-cytometry, and the comet assay. Cypermethrin at 5.13 ng/mL revealed cytotoxicity, apoptosis, oxidative stress, and genotoxicity while highlighting GM-CSF's protective properties on HFF-1. GM-CSF markedly attenuated cypermethrin-induced apoptotic cell death (early and late apoptotic rates). GM-CSF considerably regulated oxidative stress and genotoxicity by reducing the ROS and LPO levels, maintaining the status of GSH and activity of SOD, and suppressing genotoxicity in the comet assay parameters. Therefore, GM-CSF could be promising as an antioxidant, anti-apoptotic, genoprotective and cytomodulating agent.