l-Arginine Decreases Inflammation and Modulates the Nuclear Factor-κB/Matrix Metalloproteinase Cascade in Mdx Muscle Fibers

摘要: Duchenne muscular dystrophy (DMD) is a lethal, X-linked disorder associated with dystrophin deficiency that results in chronic inflammation, sarcolemma damage, and severe skeletal muscle degeneration. Recently, the use of l-arginine, substrate nitric oxide synthase (nNOS), has been proposed as pharmacological treatment to attenuate dystrophic pattern DMD. However, little known about signaling events occur l-arginine treatment. Considering implication inflammation processes, we asked whether inhibits inflammatory cascades. We demonstrate decreases enhances regeneration mdx mouse model. Classic stimulatory signals, such proinflammatory cytokines interleukin-1β, interleukin-6, tumor necrosis factor-α, are significantly decreased muscle, resulting lower nuclear factor (NF)-κB levels activity. NF-κB serves pivotal transcription multiple regulation; previous studies have shown perturbation both DMD muscle. Moreover, activity metalloproteinase (MMP)-2 MMP-9, which transcriptionally activated by NF-κB. show inhibitory effect on NF-κB/MMP cascade reduces β-dystroglycan cleavage translocates utrophin nNOS throughout sarcolemma. Collectively, our clarify molecular promotes membrane integrity suggest NF-κB-related cascades could be potential therapeutic targets for management.