title: Characterization of Quin-C1 for its anti-inflammatory property in a mouse model of bleomycin-induced lung injury.
abstract: OBJECTIVE
  To study the in vivo effects of Quin-C1, a highly specific agonist for formyl peptide receptor 2 (FPR2/ALX), in a mouse model of bleomycin (BLM)-induced lung injury.
  
  
  METHODS
  Male ICR mice were injected intratracheally with BLM (d 0), and intraperitoneally with Quin-C1 (0.2 mg/d) or vehicle between d 1 and d 28, during which pulmonary inflammation was monitored. A similar regimen was carried out between d 5 and d 28 to differentiate anti-inflammatory from anti-fibrotic effects. During the treatment, leukocyte numbers in bronchoalveolar lavage fluid (BALF) were counted, and FPR2/ALX transcripts, tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), the mouse keratinocyte-derived chemokine (KC), transforming growth factor β1 (TGF-β1) and C-X-C motif chemokine 10 (CXCL10) expression levels in the lung tissue were also measured. Both hydroxyproline content and histological changes were examined on d 28 to assess the severity of lung fibrosis.
  
  
  RESULTS
  BLM caused a significant increase in expression levels of all the selected cytokines and chemokines, as well as a thickening of the alveolar wall. Treatment with Quin-C1 significantly reduced the neutrophil and lymphocyte counts in BALF, diminished expression of TNF-α, IL-1β, KC, and TGF-β1, and decreased collagen deposition in lung tissue. The treatment also lowered the content of lung hydroxyproline. Quin-C1 did not ameliorate lung fibrosis when the treatment was started 5 d after the BLM challenge, suggesting that the protection may be attributed to its anti-inflammatory effects. Exposure to BLM or BLM plus Quin-C1 did not change the level of FPR2/ALX transcripts (mFpr1, mFpr2, and Lxa4r) in the lung tissue.
  
  
  CONCLUSIONS
  The results demonstrate an anti-inflammatory role for Quin-C1 in bleomycin-induced lung injury, which may be further explored for therapeutic applications.
authors.affiliation: The National Center for Drug Screening, the State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Min
authors.initials: M
authors.lastname: He
authors.forename: Ni
authors.initials: N
authors.lastname: Cheng
authors.forename: Wei-wei
authors.initials: WW
authors.lastname: Gao
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.forename: Yue-yun
authors.initials: YY
authors.lastname: Zhang
authors.forename: Richard D
authors.initials: RD
authors.lastname: Ye
authors.forename: Ming-wei
authors.initials: MW
authors.lastname: Wang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D001761:Bleomycin / Q000633:toxicity; D018925:Chemokines / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D055370:Lung Injury / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011799:Quinazolines / Q000494:pharmacology*; D044042:Receptors, Formyl Peptide / Q000819:agonists; D013997:Time Factors
chemical_list: C493592:4-butoxy-N-(2-(4-methoxy-phenyl)-4-oxo-1,4-dihydro-2H-quinazolin-3-yl)-benzamide; D000893:Anti-Inflammatory Agents; D001549:Benzamides; D018925:Chemokines; D016207:Cytokines; D011799:Quinazolines; D044042:Receptors, Formyl Peptide; C481578:formyl peptide receptor 2, mouse; D001761:Bleomycin