title: Interplay between Matrix Metalloproteinase-9, Matrix Metalloproteinase-2, and Interleukins in Multiple Sclerosis Patients.
abstract: Matrix Metalloproteases (MMPs) and cytokines have been involved in the pathogenesis of multiple sclerosis (MS). However, no studies have still explored the possible associations between the two families of molecules. The present study aimed to evaluate the contribution of active MMP-9, active MMP-2, interleukin- (IL-) 17, IL-18, IL-23, and monocyte chemotactic proteins-3 to the pathogenesis of MS and the possible interconnections between MMPs and cytokines. The proteins were determined in the serum and cerebrospinal fluid (CSF) of 89 MS patients and 92 other neurological disorders (OND) controls. Serum active MMP-9 was increased in MS patients and OND controls compared to healthy subjects (p < 0.001 and p < 0.01, resp.), whereas active MMP-2 and ILs did not change. CSF MMP-9, but not MMP-2 or ILs, was selectively elevated in MS compared to OND (p < 0.01). Regarding the MMPs and cytokines intercorrelations, we found a significant association between CSF active MMP-2 and IL-18 (r = 0.3, p < 0.05), while MMP-9 did not show any associations with the cytokines examined. Collectively, our results suggest that active MMP-9, but not ILs, might be a surrogate marker for MS. In addition, interleukins and MMPs might synergistically cooperate in MS, indicating them as potential partners in the disease process.
authors.affiliation: Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Alessandro
authors.identifier: 0000-0003-3579-7921
authors.initials: A
authors.lastname: Trentini
authors.affiliation: Section of Neurology, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Massimiliano
authors.identifier: 0000-0001-6555-6075
authors.initials: M
authors.lastname: Castellazzi
authors.affiliation: Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Carlo
authors.identifier: 0000-0003-4777-6300
authors.initials: C
authors.lastname: Cervellati
authors.affiliation: Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Maria Cristina
authors.identifier: 0000-0003-0174-539X
authors.initials: MC
authors.lastname: Manfrinato
authors.affiliation: Section of Neurology, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Tamborino
authors.affiliation: Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Stefania
authors.identifier: 0000-0002-2817-9941
authors.initials: S
authors.lastname: Hanau
authors.affiliation: Section of Orthopedics, Obstetrics and Gynecology and Anesthesia and Resuscitation, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Carlo Alberto
authors.identifier: 0000-0003-3533-6121
authors.initials: CA
authors.lastname: Volta
authors.affiliation: Neurology Unit, Department of Neurosciences and Rehabilitation, Azienda Ospedaliera-Universitaria, Arcispedale S. Anna, 44124 Ferrara, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Baldi
authors.affiliation: Neurology Clinic, Clinical Centre of Serbia, School of Medicine, University of Belgrade, Dr. Subotica 6, 11000 Belgrade, Serbia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kostic
authors.affiliation: Neurology Clinic, Clinical Centre of Serbia, School of Medicine, University of Belgrade, Dr. Subotica 6, 11000 Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Drulovic
authors.affiliation: Section of Neurology, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Enrico
authors.identifier: 0000-0003-4038-3192
authors.initials: E
authors.lastname: Granieri
authors.affiliation: Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Franco
authors.identifier: 0000-0002-5325-8377
authors.initials: F
authors.lastname: Dallocchio
authors.affiliation: Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Tiziana
authors.identifier: 0000-0001-7975-921X
authors.initials: T
authors.lastname: Bellini
authors.affiliation: Neurology Clinic, Clinical Centre of Serbia, School of Medicine, University of Belgrade, Dr. Subotica 6, 11000 Belgrade, Serbia.
authors.forename: Irena
authors.initials: I
authors.lastname: Dujmovic
authors.affiliation: Neuroradiology Unit, Department of Neurosciences and Rehabilitation, Azienda Ospedaliera-Universitaria, Arcispedale S. Anna, 44124 Ferrara, Italy.
authors.forename: Enrico
authors.identifier: 0000-0003-0477-724X
authors.initials: E
authors.lastname: Fainardi
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D054405:Chemokine CCL3 / Q000097:blood / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D007378:Interleukins / Q000097:blood* / Q000134:cerebrospinal fluid; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood* / Q000134:cerebrospinal fluid; D020780:Matrix Metalloproteinase 9 / Q000097:blood* / Q000134:cerebrospinal fluid; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000134:cerebrospinal fluid
chemical_list: D015415:Biomarkers; D054405:Chemokine CCL3; D007378:Interleukins; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9