title: Differential effects of dexamethasone and rosiglitazone in a sephadex-induced model of lung inflammation in rats: possible role of tissue inhibitor of metalloproteinase-3.
abstract: OBJECTIVE
  To study the effects of two different classes of drugs in sephadex-induced lung inflammation using rats and explore the potential mechanism (s).
  
  
  METHODS
  Effects of dexamethasone (0.3 mg/kg, p.o.) and rosiglitazone (10 mg/kg, p.o.) treatments were evaluated up to 3 days in sephadex challenged rats. 72 h postsephadex administration, broncho-alveolar lavage fluid (BALF) was collected for cell count and cytokine estimation. Lung tissues were harvested for gene expression and histopathology.
  
  
  RESULTS
  Dexamethasone treatment resulted in significant inhibition of lymphocytes, monocytes, eosinophils and neutrophils, whereas rosiglitazone inhibited eosinophils and neutrophils only. Further, dexamethasone reduced the elevated levels of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) after sephadex challenge while rosiglitazone significantly reduced the PGE2 levels without altering LTB4 in the BALF. Hydroxyproline content in rat lung homogenate was significantly reduced with dexamethasone treatment but not with rosiglitazone. Both the drugs were found to suppress matrix metallo proteinase 9, whereas only dexamethasone showed inhibition of tumor necrosis factor-alpha and up-regulation of tissue inhibitor of metalloproteinase 3 (TIMP-3) expression and preserved the broncho-alveolar microstructure.
  
  
  CONCLUSIONS
  Our results revealed that up-regulation of TIMP-3 corroborated well with dexamethasone mediated inhibition of collagen degradation and restoration of alveolar micro-architecture.
authors: Department of Pharmacology, Zydus Research Centre, Ahmedabad, Gujarat, India ; Department of Pharmacology, KB Institute of Pharmaceutical Education and Research, Gandhinagar, Ahmedabad, Gujarat, India.
authors: Jignesh K
authors: JK
authors: Nagar
authors: Department of Toxicology, Torrent Research Center, Ahmedabad, Gujarat, India.
authors: Praful P
authors: PP
authors: Patel
authors: Department of Pharmacology, Zydus Research Centre, Ahmedabad, Gujarat, India.
authors: Jogeswar N
authors: JN
authors: Mohapatra
authors: Department of Pharmacology, Zydus Research Centre, Ahmedabad, Gujarat, India.
authors: Manoranjan M
authors: MM
authors: Sharma
authors: Department of Animal Genetics and Breeding, College of Veterinary Science and Animal Husbandry, Navsari Agricultural University, Navsari, Gujarat, India.
authors: Gaurav M
authors: GM
authors: Pandya
authors: Department of Pharmacology, Zydus Research Centre, Ahmedabad, Gujarat, India.
authors: Malik M
authors: MM
authors: Umar
authors: Department of Pharmacology, Zydus Research Centre, Ahmedabad, Gujarat, India.
authors: Abhijit A
authors: AA
authors: Chatterjee
authors: Department of Pharmacology, KB Institute of Pharmaceutical Education and Research, Gandhinagar, Ahmedabad, Gujarat, India.
authors: Shrikalp S
authors: SS
authors: Deshpande
authors: Department of Pharmacology, Zydus Research Centre, Ahmedabad, Gujarat, India.
authors: Mukul R
authors: MR
authors: Jain
authors: Department of Pharmacology, Zydus Research Centre, Ahmedabad, Gujarat, India ; Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, USA.
authors: Hitesh M
authors: HM
authors: Soni
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D003911:Dextrans / Q000008:administration & dosage*; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D047495:PPAR gamma / Q000819:agonists; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000819:agonists; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D003911:Dextrans; D047495:PPAR gamma; D011965:Receptors, Glucocorticoid; D045162:Thiazolidinediones; D019717:Tissue Inhibitor of Metalloproteinase-3; D000077154:Rosiglitazone; D003907:Dexamethasone; C025614:sephadex; D006909:Hydroxyproline
keywords: Dexamethasone; lung inflammation; matrix metalloproteinase 9; rosiglitazone; tissue inhibitor of metalloproteinase 3