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.
Acta Pharmacol Sin. 2011 May;32(5):601-10. doi: 10.1038/aps.2011.4. Epub 2011 Apr 18.
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.
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.
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.
The results demonstrate an anti-inflammatory role for Quin-C1 in bleomycin-induced lung injury, which may be further explored for therapeutic applications.
研究高选择性福瑞肽受体 2（FPR2/ALX）激动剂 Quin-C1 在博来霉素（BLM）诱导的肺损伤小鼠模型中的体内作用。
雄性 ICR 小鼠于 d0 经气管内注射 BLM，并于 d1 至 d28 期间每日腹腔内注射 Quin-C1（0.2mg/d）或载体，在此期间监测肺部炎症。在 d5 至 d28 期间进行类似方案以区分抗炎和抗纤维化作用。在治疗过程中，计数支气管肺泡灌洗液（BALF）中的白细胞数量，并测量肺组织中 FPR2/ALX 转录物、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、鼠角质形成细胞衍生趋化因子（KC）、转化生长因子-β1（TGF-β1）和 C-X-C 基序趋化因子 10（CXCL10）的表达水平。在 d28 时检查羟脯氨酸含量和组织学变化，以评估肺纤维化的严重程度。
BLM 导致所有选定的细胞因子和趋化因子的表达水平显著增加，并导致肺泡壁增厚。Quin-C1 治疗显著降低 BALF 中的中性粒细胞和淋巴细胞计数，减少 TNF-α、IL-1β、KC 和 TGF-β1 的表达，并减少肺组织中的胶原沉积。该治疗还降低了肺羟脯氨酸含量。当在 BLM 挑战后 5 天开始治疗时，Quin-C1 并未改善肺纤维化，表明保护作用可能归因于其抗炎作用。BLM 或 BLM 加 Quin-C1 暴露并未改变肺组织中 FPR2/ALX 转录物（mFpr1、mFpr2 和 Lxa4r）的水平。
结果表明 Quin-C1 在博来霉素诱导的肺损伤中具有抗炎作用，这可能进一步探索其治疗应用。
