Erdogan Suat, Aslantas Ozkan, Celik Sefa, Atik Esin
Department of Biochemistry, Faculty of Veterinary Medicine, Mustafa Kemal University, Hatay 31034, Turkey.
Res Vet Sci. 2008 Feb;84(1):18-25. doi: 10.1016/j.rvsc.2007.02.003. Epub 2007 Mar 29.
Cyclic AMP (cAMP) is a key intracellular second messenger which at increased levels has been shown to have anti-inflammatory and tissue-protective effects. Its concentration is determined by the activities of both adenylate cyclase (AC) and the phosphodiesterase (PDE) enzymes. The aim of this study was to compare the effects of increased cAMP and glucocorticoid dexamethasone administration on B. melitensis-induced lipid peroxidation, Brucella suppressed antioxidant enzyme activities and PDE4 transcripts in rats. Intracellular cyclic AMP level was elevated by two different approaches; activation of AC and inhibition of PDE activities. Rats were inoculated with B. melitensis for seven days then a single dose of nonselective PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX), the adenylate cyclase activator forskolin and dexamethasone were administrated to each infected group, and animals were challenged for 48 h. Brucella-induced lipid peroxidation was significantly reduced by the cAMP elevating agents as well as dexamethasone administration in plasma, liver and spleen. The antioxidant enzymes glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were significantly decreased by the pathogen. Whilst suppressed GSH-Px activity was reversed by cAMP elevating agents, SOD activity was not restored. Superoxide generating enzyme xanthine oxidase activity was not altered at the end of the infection period. Brucella infection increased plasma IL-12 level and this effect was also suppressed by the cAMP elevating agents, whereas TNF-alpha, IFN-gamma and IL-10 levels were unchanged. Intracellular cAMP levels are entirely hydrolyzed by cAMP-specific PDE 4 isozymes (PDE4s) in inflammatory and immunocompetent cells. Brucella reduced mRNA transcript levels for PDE4A by 40%, though PDE4B and 4D transcriptions were being unaffected in spleen. It was concluded that B. melitensis infection decreased activity of the antioxidant defence system, induced lipid peroxidation and suppressed PDE4A transcription. Administration of cAMP elevating agents exhibited similar affect with dexamethasone on lipid peroxidation, IL-12 production and antioxidant enzyme activities in Brucella infection.
环磷酸腺苷（cAMP）是一种关键的细胞内第二信使，其水平升高已被证明具有抗炎和组织保护作用。其浓度由腺苷酸环化酶（AC）和磷酸二酯酶（PDE）的活性共同决定。本研究的目的是比较增加cAMP和给予糖皮质激素地塞米松对大鼠中布鲁氏菌诱导的脂质过氧化、布鲁氏菌抑制的抗氧化酶活性及PDE4转录本的影响。通过两种不同方法提高细胞内环磷酸腺苷水平：激活AC和抑制PDE活性。大鼠接种布鲁氏菌7天，然后给每个感染组单次给予非选择性PDE抑制剂3-异丁基-1-甲基黄嘌呤（IBMX）、腺苷酸环化酶激活剂福斯可林和地塞米松，并对动物进行48小时的攻击。cAMP升高剂以及地塞米松给药可显著降低布鲁氏菌诱导的血浆、肝脏和脾脏中的脂质过氧化。病原体可显著降低抗氧化酶谷胱甘肽过氧化物酶（GSH-Px）和超氧化物歧化酶（SOD）的活性。虽然cAMP升高剂可逆转被抑制的GSH-Px活性，但SOD活性未恢复。感染期末超氧化物生成酶黄嘌呤氧化酶活性未改变。布鲁氏菌感染可增加血浆IL-12水平，而这种作用也被cAMP升高剂所抑制，而肿瘤坏死因子-α、干扰素-γ和白细胞介素-10水平未改变。在炎症和免疫活性细胞中，细胞内环磷酸腺苷水平完全由cAMP特异性PDE 4同工酶（PDE4s）水解。布鲁氏菌使脾脏中PDE4A的mRNA转录水平降低了40%，而PDE4B和4D的转录未受影响。得出的结论是，布鲁氏菌感染降低了抗氧化防御系统的活性，诱导了脂质过氧化并抑制了PDE4A转录。在布鲁氏菌感染中，给予cAMP升高剂对地塞米松在脂质过氧化、IL-12产生和抗氧化酶活性方面表现出相似的影响。
