title: Increased calpain correlates with Th1 cytokine profile in PBMCs from MS patients.
abstract: Multiple sclerosis (MS) is a devastating autoimmune demyelinating disease of the central nervous system (CNS). This study investigated whether expression and activity of the calcium-activated protease calpain correlated with Th1/Th2 dysregulation in MS patients during states of relapse and remission. Calpain expression and activity were significantly increased in peripheral blood mononuclear cells (PBMCs) from MS patients, compared to controls, with the highest expression and activity noted during relapse. Th1 cytokines were highest and Th2 cytokines were lowest in MS patients during relapse. Treatment with calpain inhibitor, calpeptin, decreased Th1 cytokines in PBMCs from MS patients. Calpain inhibitor also reduced degradation of myelin basic protein (MBP) by inhibiting the calpain secreted from MBP-specific T cells. Taken together, these results suggested calpain involvement in Th1/Th2 dysregulation in MS patients.
authors.affiliation: Department of Neurosciences, Division of Neurology, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Imam
authors.forename: Mary K
authors.initials: MK
authors.lastname: Guyton
authors.forename: Azizul
authors.initials: A
authors.lastname: Haque
authors.forename: Arthur
authors.initials: A
authors.lastname: Vandenbark
authors.forename: William R
authors.initials: WR
authors.lastname: Tyor
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Ray
authors.forename: Naren L
authors.initials: NL
authors.lastname: Banik
mesh_terms: D015415:Biomarkers / Q000032:analysis / Q000097:blood; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000276:immunology; D002154:Calpain / Q000037:antagonists & inhibitors / Q000097:blood / Q000276:immunology*; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D004151:Dipeptides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D004676:Myelin Basic Protein / Q000187:drug effects / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D012008:Recurrence; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
chemical_list: D015415:Biomarkers; D016207:Cytokines; D004151:Dipeptides; D004791:Enzyme Inhibitors; D004676:Myelin Basic Protein; C071482:calpeptin; D002154:Calpain; D002118:Calcium