RGD Reference Report - The effects of increased cAMP content on inflammation, oxidative stress and PDE4 transcripts during Brucella melitensis infection. - Rat Genome Database

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The effects of increased cAMP content on inflammation, oxidative stress and PDE4 transcripts during Brucella melitensis infection.

Authors: Erdogan, S  Aslantas, O  Celik, S  Atik, E 
Citation: Erdogan S, etal., Res Vet Sci. 2008 Feb;84(1):18-25. Epub 2007 Mar 29.
RGD ID: 2302429
Pubmed: PMID:17397885   (View Abstract at PubMed)
DOI: DOI:10.1016/j.rvsc.2007.02.003   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PDE4AHumanbrucellosis  ISOPde4a (Rattus norvegicus)mRNA:decreased expression:spleenRGD 
Pde4aRatbrucellosis  IEP mRNA:decreased expression:spleenRGD 
Pde4aMousebrucellosis  ISOPde4a (Rattus norvegicus)mRNA:decreased expression:spleenRGD 

Objects Annotated

Genes (Rattus norvegicus)
Pde4a  (phosphodiesterase 4A)

Genes (Mus musculus)
Pde4a  (phosphodiesterase 4A, cAMP specific)

Genes (Homo sapiens)
PDE4A  (phosphodiesterase 4A)


Additional Information