title: Sulforaphane Attenuates Muscle Inflammation in Dystrophin-deficient mdx Mice via NF-E2-related Factor 2 (Nrf2)-mediated Inhibition of NF-κB Signaling Pathway.
abstract: Inflammation is widely distributed in patients with Duchenne muscular dystrophy and ultimately leads to progressive deterioration of muscle function with chronic muscle damage, oxidative stress, and reduced oxidative capacity. NF-E2-related factor 2 (Nrf2) plays a critical role in defending against inflammation in different tissues via activation of phase II enzyme heme oxygenase-1 and inhibition of the NF-κB signaling pathway. However, the role of Nrf2 in the inflammation of dystrophic muscle remains unknown. To determine whether Nrf2 may counteract inflammation in dystrophic muscle, we treated 4-week-old male mdx mice with the Nrf2 activator sulforaphane (SFN) by gavage (2 mg/kg of body weight/day) for 4 weeks. The experimental results demonstrated that SFN treatment increased the expression of muscle phase II enzyme heme oxygenase-1 in an Nrf2-dependent manner. Inflammation in mice was reduced by SFN treatment as indicated by decreased infiltration of immune cells and expression of the inflammatory cytokine CD45 and proinflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the skeletal muscles of mdx mice. In addition, SFN treatment also decreased the expression of NF-κB(p65) and phosphorylated IκB kinase-α as well as increased inhibitor of κB-α expression in mdx mice in an Nrf2-dependent manner. Collectively, these results show that SFN-induced Nrf2 can alleviate muscle inflammation in mdx mice by inhibiting the NF-κB signaling pathway.
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, 430071 Wuhan, China.
authors.forename: Cheng-Cao
authors.initials: CC
authors.lastname: Sun
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, 430071 Wuhan, China.
authors.forename: Shu-Jun
authors.initials: SJ
authors.lastname: Li
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, 430071 Wuhan, China.
authors.forename: Cui-Li
authors.initials: CL
authors.lastname: Yang
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, 430071 Wuhan, China.
authors.forename: Rui-Lin
authors.initials: RL
authors.lastname: Xue
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, 430071 Wuhan, China.
authors.forename: Yong-Yong
authors.initials: YY
authors.lastname: Xi
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, 430071 Wuhan, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Lanzhou University, 730000 Lanzhou, China.
authors.forename: Qian-Long
authors.initials: QL
authors.lastname: Zhao
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, 430071 Wuhan, China. Electronic address: lodjlwhu@sina.com.
authors.forename: De-Jia
authors.initials: DJ
authors.lastname: Li
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D016189:Dystrophin / Q000235:genetics*; D017353:Gene Deletion; D051547:Heme Oxygenase-1 / Q000276:immunology; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D051267:NF-E2-Related Factor 2 / Q000819:agonists / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology*; D018384:Oxidative Stress; D015398:Signal Transduction / Q000187:drug effects; D013454:Sulfoxides
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016189:Dystrophin; D017879:Isothiocyanates; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D013454:Sulfoxides; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C016766:sulforaphane
keywords: NF-κB; antioxidant; inflammation; nuclear translocation; oxidative stress; transcription factor; transgenic mice