601. The monoacylglycerol lipase inhibitor JZL184 decreases inflammatory response in skeletal muscle contusion in rats
- Author
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Meng-Zhou Zhang, Lin-Lin Wang, Da-Wei Guan, Zhi-Ling Tian, Shan-Shan Li, Jiao-Yong Li, Miao Zhang, Min Liu, Shu-Kun Jiang, Rui Zhao, and Meng Wang
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,Neutrophils ,medicine.medical_treatment ,Contusions ,Anti-Inflammatory Agents ,Inflammation ,Lung injury ,Collagen Type I ,Rats, Sprague-Dawley ,Receptor, Cannabinoid, CB2 ,chemistry.chemical_compound ,Piperidines ,Receptor, Cannabinoid, CB1 ,Internal medicine ,medicine ,Cannabinoid receptor type 2 ,Myocyte ,Animals ,Benzodioxoles ,RNA, Messenger ,Enzyme Inhibitors ,Muscle, Skeletal ,Cannabinoid Receptor Antagonists ,JZL184 ,Pharmacology ,Wound Healing ,Myositis ,Chemistry ,Macrophages ,Skeletal muscle ,Fibroblasts ,Fibrosis ,Monoacylglycerol Lipases ,Monoacylglycerol lipase ,Collagen Type I, alpha 1 Chain ,Disease Models, Animal ,Endocrinology ,medicine.anatomical_structure ,Collagen Type III ,Biochemistry ,Neutrophil Infiltration ,Cytokines ,Cannabinoid ,medicine.symptom ,Inflammation Mediators ,Signal Transduction - Abstract
Muscle wound healing process is a typical inflammation-evoked event. The monoacylglycerol lipase (MAGL) inhibitor (4-nitrophenyl)4-[bis(1,3-benzodioxol -5-yl)-hydroxymethyl]piperidine-1-carboxylate (JZL184) has been previously reported to reduce inflammation in colitis and acute lung injury in mice, which provide a new strategy for primary care of skeletal muscle injury. We investigated the effect of JZL184 on inflammation in rat muscle contusion model, and found decreased neutrophil and macrophage infiltration and pro-inflammatory cytokine expression. With extension of post-traumatic interval, myofiber regeneration was significantly hindered with increased collagen types I and ІІІ mRNAfibroblast infiltration as well as promoted fibrosis. Furthermore, 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-morpholin-4-ylpyrazole-3-carboxamide (AM281, a selective cannabinoid CB1 receptor antagonist) and [6-iodo-2-methyl-1-(2-morpholin-4-ylethyl)indol-3-yl]-(4-methoxyphenyl)methanone (AM630, a selective cannabinoid CB2 receptor antagonist) treatment alleviated the anti-inflammatory effect of JZL184. Our findings demonstrate that JZL184 is able to inhibit the inflammatory response and interfere with contused muscle healing, in which the anti-inflammatory action may be mediated through cannabinoid CB1 and CB2 receptors.
- Published
- 2015