CGS 21680, an agonist of the adenosine (A2A) receptor, decreases acute lung inflammation
CGS 21680, an agonist of the adenosine (A2A) receptor, decreases acute lung inflammation
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DOI：
10.1016/j.ejphar.2011.06.049
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发表时间：
2011-10-01
影响因子：
5
通讯作者：
Cuzzocrea, Salvatore
中科院分区：
文献类型：
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作者：
Impellizzeri, Daniela;Di Paola, Rosanna;Cuzzocrea, Salvatore
腺苷A(2A)受体激动剂可能是重要的炎症调节剂。本研究的目的是观察腺苷(A(2A))受体激动剂CGS0.1 mg/kg对角叉菜胶致胸膜炎小鼠模型的影响。胸腔内注射角叉菜胶致小鼠急性炎症反应，其特征是：中性粒细胞在肺组织中的浸润和随后的脂质过氧化反应，一氧化氮(NO)、细胞因子如肿瘤坏死因子-α(TNF-α)和白介素1-β(IL-1β)的产生增加，以及细胞间黏附分子(ICAM-1)和血小板黏附分子(P-选择素)的表达增加。此外，角叉菜胶能诱导肺组织核因子-kappaB、诱导型一氧化氮合酶、硝基酪氨酸的表达，激活多聚腺苷二磷酸核糖聚合酶(PARP)，并诱导细胞凋亡(Fas配体表达、Bax和Bcl2表达)。在用角叉菜胶激发前30分钟给予CGS 21680可显著降低所有测量的炎症参数。此外，为了证实CGS 21680的抗炎作用，我们还评估了CGS 21680的治疗后(角叉菜胶致伤后30min)的作用，并证明它还能减少中性粒细胞的浸润，减轻肺损伤程度。因此，基于这些发现，我们建议腺苷A(2A)受体激动剂，如CGS 21680，可能在治疗各种炎症性疾病方面有用。(C)2011爱思唯尔B.V.保留所有权利。
Adenosine A(2A) receptor agonists may be important regulators of inflammation. The aim of this study was to investigate the effects of CGS 21680 (0.1 mg/kg i.p.), an agonist of the adenosine (A(2A)) receptor, in a mouse model of carrageenan-induced pleurisy. Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterised by: infiltration of neutrophils in lung tissues and subsequent lipid peroxidation, increased production of nitric oxide (NO), cytokines such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) and increased expression of intercellular adhesion molecule (ICAM-1) and platelet-adhesion molecule (P-selectin). Furthermore, carrageenan induced the expression of nuclear factor-kappa B (NF-kappa B), inducible nitric oxide synthase (iNOS), nitrotyrosine, the activation of poly-ADP-ribosyl polymerase ( PARP), as well as induced apoptosis (FAS-ligand expression, Bax and Bcl-2 expression) in the lung tissues. Administration of CGS 21680, 30 min prior to challenge with carrageenan, caused a significant reduction of all the parameters of inflammation measured. In addition, to confirm the anti-inflammatory effect of CGS 21680, we have also evaluated the effects of CGS 21680 post-treatment (30 min after the challenge with carrageenan) and we have demonstrated that also it caused a reduction of neutrophil infiltration and the degree of lung injury. Thus, based on these findings we propose that adenosine A(2A) receptor agonists such as CGS 21680 may be useful in the treatment of various inflammatory diseases. (C) 2011 Elsevier B.V. All rights reserved.