title: Alpha glucocorticoid receptor expression in different experimental rat models of acute lung injury.
abstract: OBJECTIVE
  Acute respiratory distress syndrome (ARDS) is a frequent form of hypoxiemic respiratory failure caused by the acute development of diffuse lung inflammation. Dysregulated systemic inflammation with persistent elevation of circulating inflammatory cytokines is the pathogenetic mechanism for pulmonary and extrapulmonary organ dysfunction in patients with ARDS. Glucocorticoids (GCs) have a broad range of inhibitory inflammatory effects, including inhibition of cytokines transcription, cellular activation and growth factor production. They inhibit the inflammatory pathways through two specific intracellular glucocorticoid receptors (GRs), named GR alpha and GR beta. The aim of our study was to evaluate the histologic evidence of inflammatory injury and the GR alpha uptake of resident and inflammatory cells in different experimental models of acute lung injury (ALI).
  
  
  METHODS
  We studied four groups of rats: three different experimental rat models of lung injury and a control group. The ALI was caused by barotrauma (due to an overventilation), oleic acid injection and mechanical ventilation. Results were compared to nonventilated rat control group. The duration of mechanical ventilation was of 2.5h. At the end of each experiment, rats were sacrificed. Lung biopsies were evaluated for morphologic changes. The immunohistochemistry was performed to study GR alpha expression.
  
  
  RESULTS
  Histologic evidence of lung injury (alveolar and interstitial edema, vascular congestion, alveolar haemorrhage, emphysema, number of interstitial cells and neutrophils, and destruction of alveolar attachments) were present in all ventilated groups. Barotrauma lead to an additional inflammatory response. GR alpha expression significantly increased in the three ventilated groups compared with nonventilated groups. GR alpha expression was highest in barotrauma group.
  
  
  CONCLUSIONS
  These data indicate that ALI is associated with diffuse alveolar damage, up-regulation of the inflammatory response and GR alpha overexpression. Barotrauma is the most effective mechanism inducing acute lung inflammation and GR alpha overexpression.
authors.affiliation: Dipartimento di Clinica Medica, Nefrologia e Scienze della Prevenzione, University of Parma, Italy. giusi@unipr.it <giusi@unipr.it>
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Bertorelli
authors.forename: Alberto
authors.initials: A
authors.lastname: Pesci
authors.forename: Silvia
authors.initials: S
authors.lastname: Peveri
authors.forename: Mario
authors.initials: M
authors.lastname: Mergoni
authors.forename: Attilio
authors.initials: A
authors.lastname: Corradi
authors.forename: Anna
authors.initials: A
authors.lastname: Maria Cantoni
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tincani
authors.forename: Antonio
authors.initials: A
authors.lastname: Bobbio
authors.forename: Michele
authors.initials: M
authors.lastname: Rusca
authors.forename: Paolo
authors.initials: P
authors.lastname: Carbognani
mesh_terms: D000818:Animals; D001469:Barotrauma / Q000150:complications; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D019301:Oleic Acid; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis*; D012121:Respiration, Artificial / Q000009:adverse effects; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000378:metabolism*
chemical_list: D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; D019301:Oleic Acid