The monoacylglycerol lipase inhibitor JZL184 decreases inflammatory response in skeletal muscle contusion in rats.
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.
Department of Forensic Pathology, China Medical University School of Forensic Medicine, Shenyang, Liaoning Province, PR China.
Shu-Kun
SK
Jiang
Department of Forensic Pathology, China Medical University School of Forensic Medicine, Shenyang, Liaoning Province, PR China.
Miao
M
Zhang
Department of Forensic Pathology, China Medical University School of Forensic Medicine, Shenyang, Liaoning Province, PR China.
Zhi-Ling
ZL
Tian
Department of Forensic Pathology, China Medical University School of Forensic Medicine, Shenyang, Liaoning Province, PR China.
Meng
M
Wang
Department of Forensic Pathology, China Medical University School of Forensic Medicine, Shenyang, Liaoning Province, PR China.
Rui
R
Zhao
Department of Forensic Pathology, China Medical University School of Forensic Medicine, Shenyang, Liaoning Province, PR China.
Lin-Lin
LL
Wang
Department of Forensic Pathology, China Medical University School of Forensic Medicine, Shenyang, Liaoning Province, PR China.
Shan-Shan
SS
Li
Department of Forensic Pathology, China Medical University School of Forensic Medicine, Shenyang, Liaoning Province, PR China.
Min
M
Liu
Department of Forensic Pathology, China Medical University School of Forensic Medicine, Shenyang, Liaoning Province, PR China.
Jiao-Yong
JY
Li
Department of Forensic Pathology, China Medical University School of Forensic Medicine, Shenyang, Liaoning Province, PR China.
Meng-Zhou
MZ
Zhang
Department of Forensic Pathology, China Medical University School of Forensic Medicine, Shenyang, Liaoning Province, PR China. Electronic address: dwguan@mail.cmu.edu.cn.
Da-Wei
DW
Guan
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D052117:Benzodioxoles / Q000494:pharmacology*; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D003288:Contusions / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D008994:Monoacylglycerol Lipases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D009220:Myositis / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D052117:Benzodioxoles; C577828:COL3A1 protein, rat; D063387:Cannabinoid Receptor Antagonists; C543264:Cnr1 protein, rat; C469526:Cnr2 protein, rat; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III; D016207:Cytokines; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; C534333:JZL 184; D010880:Piperidines; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D008994:Monoacylglycerol Lipases
AM281 (PubChem CID: 4302962); AM630 (PubChem CID: 4302963); Fibrosis; Inflammation; JZL184 (PubChem CID: 25021165); Monoacylglycerol lipase; Skeletal muscle injury; Wound repair