title: CB2 receptor activation ameliorates the proinflammatory activity in acute lung injury induced by paraquat.
abstract: Paraquat, a widely used herbicide, is well known to exhibit oxidative stress and lung injury. In the present study, we investigated the possible underlying mechanisms of cannabinoid receptor-2 (CB2) activation to ameliorate the proinflammatory activity induced by PQ in rats. JWH133, a CB2 agonist, was administered by intraperitoneal injection 1 h prior to PQ exposure. After PQ exposure for 4, 8, 24, and 72 h, the bronchoalveolar lavage fluid was collected to determine levels of TNF-α and IL-1β, and the arterial blood samples were collected for detection of PaO2 level. At 72 h after PQ exposure, lung tissues were collected to determine the lung wet-to-dry weight ratios, myeloperoxidase activity, lung histopathology, the protein expression level of CB2, MAPKs (ERK1/2, p38MAPK, and JNK1/2), and NF-κBp65. After rats were pretreated with JWH133, PQ-induced lung edema and lung histopathological changes were significantly attenuated. PQ-induced TNF-α and IL-1β secretion in BALF, increases of PaO2 in arterial blood, and MPO levels in the lung tissue were significantly reduced. JWH133 could efficiently activate CB2, while inhibiting MAPKs and NF-κB activation. The results suggested that activating CB2 receptor exerted protective activity against PQ-induced ALI, and it potentially contributed to the suppression of the activation of MAPKs and NF-κB pathways.
authors: Department of Emergency Medicine, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning 110004, China.
authors: Zhenning
authors: Z
authors: Liu
authors: Department of Emergency Medicine, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning 110004, China.
authors: Yu
authors: Y
authors: Wang
authors: Department of Emergency Medicine, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning 110004, China.
authors: Hongyu
authors: H
authors: Zhao
authors: Department of Emergency Medicine, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning 110004, China.
authors: Qiang
authors: Q
authors: Zheng
authors: Department of Emergency Medicine, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning 110004, China.
authors: Li
authors: L
authors: Xiao
authors: Department of Emergency Medicine, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning 110004, China.
authors: Min
authors: M
authors: Zhao
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006540:Herbicides / Q000009:adverse effects* / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010269:Paraquat / Q000009:adverse effects* / Q000494:pharmacology; D011654:Pulmonary Edema / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002186:Cannabinoids; D006540:Herbicides; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D016328:NF-kappa B; D043885:Receptor, Cannabinoid, CB2; D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases; D010269:Paraquat; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC