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Effects of endocrine active contaminating pesticides on RACK1 expression and immunological consequences in THP-1 cells
Affiliation:1. Laboratory of Toxicology, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università Degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy;2. Dipartimento di Scienze del Farmaco, Università Degli Studi di Pavia, Viale Taramelli 12/14, 27100 Pavia, Italy;3. Scuola Universitaria Superiore IUSS, Piazza della Vittoria 15, 27100 Pavia, Italy;4. Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA;1. School of Public Health, Southwest Medical University, Luzhou 646000, China;2. Department of Clinical Laboratory, 404 Hospital of Mianyang, Mianyang 621000, China;3. School of Pharmacy, Southwest Medical University, Luzhou 646000, China;4. State Key Laboratory of Coal Mine Disaster Dynamics and Control, Chongqing University, Chongqing 400044, China;5. School of Environmental and Resource, Southwest University of Science and Technology, Mianyang 621010, China;1. Toxicology laboratory, Raymond Poincaré hospital, AP-HP, Garches, France;2. MasSpecLab Platform, UMR1173, Inserm, Montigny-le-Bretonneux, France;3. Department of Forensic Medicine and Pathology, Raymond Poincaré Hospital, AP-HP, Garches, France;4. Paris Ouest Research Clinic Unit, Ambroise Paré hospital, AP-HP, Boulogne-Billancourt, France;1. Laboratory of Pharmacology, Chulabhorn Research Institute, Thailand;2. Translational Research Unit, Chulabhorn Research Institute, 54 KamphaengPhet6 Rd, Bangkok 10210 Thailand;3. Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI, Thailand;4. Chulabhorn Graduate Institute, 906 KamphaengPhet6 Rd, Bangkok, 10210 Thailand
Abstract:
We have previously demonstrated that RACK1, which expression is under steroid hormone control, plays an important role in the activation of immune cells and its expression can be useful to evaluate the immunotoxic profile of endocrine disrupting chemicals (EDCs). Hence, we investigated the effects of three contaminating and persistent pesticides: the fungicide vinclozolin (VIN), the herbicide atrazine (ATR) and the insecticide cypermethrin (CYP) on RACK1 expression and on innate immune response. VIN resulted in modest alteration of RACK1 while ATR and CYP reduced in a dose dependent manner RACK1 expression, ultimately leading to the decrease in lipopolysaccharide‐induced IL‐8 and TNF-α release and CD86 and CD54 surface marker expression. Moreover, our data indicate that, after exposure to EDCs, alterations of RACK1 expression can also occur with mechanisms not directly mediated by an interaction with a nuclear or membrane steroid receptors. Therefore, RACK1 could represent a useful EDCs screening tool to evaluate their immunotoxic potential and to dissect their mechanisms of action.
Keywords:Endocrine disrupting chemicals (EDCs)  Immunotoxicity  RACK1  Vinclozolin  Atrazine  Cypermethrin
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