RGD Reference Report - Successful treatment of acute lung injury with pitavastatin in septic mice: potential role of glucocorticoid receptor expression in alveolar macrophages. - Rat Genome Database

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Successful treatment of acute lung injury with pitavastatin in septic mice: potential role of glucocorticoid receptor expression in alveolar macrophages.

Authors: Takano, K  Yamamoto, S  Tomita, K  Takashina, M  Yokoo, H  Matsuda, N  Takano, Y  Hattori, Y 
Citation: Takano K, etal., J Pharmacol Exp Ther. 2011 Feb;336(2):381-90. Epub 2010 Nov 5.
RGD ID: 4892317
Pubmed: PMID:21057058   (View Abstract at PubMed)
DOI: DOI:10.1124/jpet.110.171462   (Journal Full-text)

There is growing evidence that the HMG-CoA reductase inhibitors (statins) provide some of the beneficial effects that are independent of their lipid-lowering effects. Recent animal experiments and clinical trials suggest that statin use may limit the development of sepsis and associated systemic inflammation. The aim of this study was to explore the potential role of statins in the prevention treatment of sepsis-induced acute lung injury (ALI). Mice were rendered septic by cecal ligation and puncture (CLP). An intraperitoneal injection of 3 mg/kg per day of pitavastatin was initiated 4 days before surgery and was maintained for life support afterward, which significantly improved the survival of CLP mice. Treatment with pitavastatin prevented the ALI development in CLP mice, as indicated by the findings that severe hypoxemia, increased pulmonary vascular permeability, and histological lung damage, including inflammatory cell infiltrate, were greatly remedied. This was associated with down-regulation of increased activity of nuclear factor-kappaB (NF-kappaB) in septic lungs. Although plasma cortisol showed a sharp rise, glucocorticoid receptor (GCR) expression in the lungs was strikingly reduced after the onset of CLP-induced sepsis. It is noteworthy that pitavastatin increased GCR expression with an increase in alveolar macrophages in which GCRs are localized, without modifying the sepsis-associated rise in plasma cortisol. These results confirm significant protection by pitavastatin on septic ALI and demonstrate that down-regulated NF-kappaB activation associated with the GCR expression increase consequent to the increased number of alveolar macrophages may explain, in part, the mechanisms responsible for favorable effects of statins on the ALI management.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NR3C1HumanSepsis  ISONr3c1 (Mus musculus)protein:decreased expression:alveolar macrophageRGD 
Nr3c1RatSepsis  ISONr3c1 (Mus musculus)protein:decreased expression:alveolar macrophageRGD 
Nr3c1MouseSepsis  IEP protein:decreased expression:alveolar macrophageRGD 

Objects Annotated

Genes (Rattus norvegicus)
Nr3c1  (nuclear receptor subfamily 3, group C, member 1)

Genes (Mus musculus)
Nr3c1  (nuclear receptor subfamily 3, group C, member 1)

Genes (Homo sapiens)
NR3C1  (nuclear receptor subfamily 3 group C member 1)


Additional Information