CB2 Receptor as Emerging Anti-Inflammatory Target in Duchenne Muscular Dystrophy

Abstract

Duchenne Muscular Dystrophy (DMD) is a very severe X-linked dystrophinopathy. It is due to a mutation in the DMD gene and causes muscular degeneration in conjunction with several secondary co-morbidities, such cardiomyopathy and respiratory failure. DMD is characterized by a chronic inflammatory state, and corticosteroids represent the main therapy for these patients. To contradict drug-related side effects, there is need for novel and more safe therapeutic strategies. Macrophages are immune cells stringently involved in both physiological and pathological inflammatory processes. They express the CB2 receptor, one of the main elements of the endocannabinoid system, and have been proposed as an anti-inflammatory target in several inflammatory and immune diseases. We observed a lower expression of the CB2 receptor in DMD-associated macrophages, hypothesizing its involvement in the pathogenesis of this pathology. Therefore, we analyzed the effect of JWH-133, a CB2 receptor selective agonist, on DMD-associated primary macrophages. Our study describes the beneficial effect of JWH-133 in counteracting inflammation by inhibiting pro-inflammatory cytokines release and by directing macrophages’ phenotype toward the M2 anti-inflammatory one.

Cannabinoid CB2 receptors enhance high-fat diet evoked peripheral neuroinflammation

“…anti-hyperalgesia in periphery. Such CB2-mediated anti-inflammatory effect has been observed in models of neuropathic and inflammatory pain[15], rheumatoid arthritis[16], multiple schlerosis[17], Duchenne Muscular Dystrophy[18] and even more[19]. Our previous study using CB2 knockout animals showed that lack of CB2 signaling exacerbates neuroinflammation[5–7], which supports anti-inflammatory role of CB2 receptors.…”

Molecular Advances on Cannabinoid and Endocannabinoid Research

“…In this respect, the pathogenesis of Duchenne Muscular Dystrophy (DMD), an X-linked dystrophinopathy due to a mutation in the DMS gene encoding for dystrophin, is characterized by muscular degeneration in conjunction with several secondary co-morbidities, such as cardiomyopathy, respiratory failure, and chronic inflammatory states [ 21 ]. Argenziano et al [ 22 ] analyzed the effect of the CB2 agonist JWH-133 on DMD-associated primary macrophages, revealing that the pharmacological activation of CB2 counteracts inflammation by inhibiting the release of pro-inflammatory cytokines and by directing the phenotype of macrophages toward anti-inflammatory and immunosuppressive activities (i.e., M2 status). Hence, the authors highlight the promising possibility to target CB2 in DMD as an additional and effective anti-inflammatory therapy.…”