title: Doxycycline Inhibits IL-17-Stimulated MMP-9 Expression by Downregulating ERK1/2 Activation: Implications in Myogenic Differentiation.
abstract: Interleukin 17 (IL-17) is a cytokine with pleiotropic effects associated with several inflammatory diseases. Although elevated levels of IL-17 have been described in inflammatory myopathies, its role in muscle remodeling and regeneration is still unknown. Excessive extracellular matrix degradation in skeletal muscle is an important pathological consequence of many diseases involving muscle wasting. In this study, the role of IL-17 on the expression of matrix metalloproteinase- (MMP-) 9 in myoblast cells was investigated. The expression of MMP-9 after IL-17 treatment was analyzed in mouse myoblasts C2C12 cell line. The increase in MMP-9 production by IL-17 was concomitant with its capacity to inhibit myogenic differentiation of C2C12 cells. Doxycycline (Doxy) treatment protected the myogenic capacity of myoblasts from IL-17 inhibition and, moreover, increased myotubes hypertrophy. Doxy blocked the capacity of IL-17 to stimulate MMP-9 production by regulating IL-17-induced ERK1/2 MAPK activation. Our results imply that MMP-9 mediates IL-17's capacity to inhibit myoblast differentiation during inflammatory diseases and indicate that Doxy can modulate myoblast response to inflammatory induction by IL-17.
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Dr. Subotića 4, 11129 Belgrade, Serbia.
authors.forename: Hristina
authors.initials: H
authors.lastname: Obradović
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Dr. Subotića 4, 11129 Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Krstić
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Dr. Subotića 4, 11129 Belgrade, Serbia.
authors.forename: Tamara
authors.initials: T
authors.lastname: Kukolj
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Dr. Subotića 4, 11129 Belgrade, Serbia.
authors.forename: Drenka
authors.identifier: 0000-0001-7041-3917
authors.initials: D
authors.lastname: Trivanović
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Dr. Subotića 4, 11129 Belgrade, Serbia.
authors.forename: Ivana Okić
authors.initials: IO
authors.lastname: Đorđević
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Dr. Subotića 4, 11129 Belgrade, Serbia.
authors.forename: Slavko
authors.identifier: 0000-0002-4399-6720
authors.initials: S
authors.lastname: Mojsilović
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Dr. Subotića 4, 11129 Belgrade, Serbia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Jauković
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Dr. Subotića 4, 11129 Belgrade, Serbia.
authors.forename: Gordana
authors.initials: G
authors.lastname: Jovčić
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Dr. Subotića 4, 11129 Belgrade, Serbia.
authors.forename: Diana
authors.identifier: 0000-0002-2629-5471
authors.initials: D
authors.lastname: Bugarski
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Dr. Subotića 4, 11129 Belgrade, Serbia.
authors.forename: Juan Francisco
authors.identifier: 0000-0001-9951-8990
authors.initials: JF
authors.lastname: Santibañez
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D004318:Doxycycline / Q000737:chemistry*; D005786:Gene Expression Regulation; D007249:Inflammation; D020381:Interleukin-17 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: C098680:Il17a protein, mouse; D020381:Interleukin-17; D011994:Recombinant Proteins; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D004318:Doxycycline