Abstract
Aim:
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.
Conclusion:
The results demonstrate an anti-inflammatory role for Quin-C1 in bleomycin-induced lung injury, which may be further explored for therapeutic applications.
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Acknowledgements
We are indebted to Xiang MENG, Xiao-yan WU, and Hao-ran SU for technical assistance. This work was supported in part by grants from the Ministry of Science and Technology of China (2009ZX09302-001), Shanghai Municipality government (08430703200 and 09DZ2291200) and the National Institutes of Health, USA (AI033503).
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Effects of late administration of Quin-C1 on BLM-induced lung injury in mice. (DOC 204 kb)
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He, M., Cheng, N., Gao, Ww. et al. Characterization of Quin-C1 for its anti-inflammatory property in a mouse model of bleomycin-induced lung injury. Acta Pharmacol Sin 32, 601–610 (2011). https://doi.org/10.1038/aps.2011.4
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DOI: https://doi.org/10.1038/aps.2011.4
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