Protective Effects of Leukadherin1 in a Rat Model of Targeted Experimental Autoimmune Encephalomyelitis (EAE): Possible Role of P47phox and MDA Downregulation

Sara Hemmati,1– 3,* Mohammad Amin Sadeghi,1– 3,* Hasan Yousefi-Manesh,2,3 Mostafa Eslamiyeh,4 Ali Vafaei,2,3 Laleh Foroutani,2 Ghazaleh Donyadideh,4 AhmadReza Dehpour,3 Nima Rezaei5– 7 1Molecular Medicine Interest Group (MMIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran; 2School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; 3Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; 4Mashhad University of Medical Sciences, Mashhad, Iran; 5Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran; 6Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; 7Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran*These authors contributed equally to this workCorrespondence: Nima Rezaei Dr Qarib St, Keshavarz Blvd, Tehran 14194, IranEmail rezaei_nima@yahoo.comAhmadReza DehpourDepartment of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, IranEmail dehpour@yahoo.comBackground: Reactive oxygen and nitrogen species (ROS and RNS) are involved in pathologic mechanisms underlying demyelination and exacerbation in multiple sclerosis (MS) lesions. P47phox is the most important subunit of an ROS-producing enzyme (NADPH oxidase) which is reportedly upregulated in MS plaques due to the intense activity of infiltrated immune cells and resident microglia. Leukadherin1 is a specific CD11b/CD18 agonist that inhibits signaling and transmigration of inflammatory cells to sites of injury. Based on this mechanism, we evaluated therapeutic effects of leukadherin1 in an animal model of targeted experimental autoimmune encephalomyelitis (EAE) through focal injection of inflammatory cytokines to the spinal cord.Methods: For model induction, Lewis rats