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Porcine CXCR1/2 antagonist CXCL8(3-72)G31P inhibits lung inflammation in LPS-challenged mice.
Scientific Reports ( IF 3.8 ) Pub Date : 2020-01-27 , DOI: 10.1038/s41598-020-57737-w Xue Wang 1 , Yanchuan Li 1 , Lintao Li 1 , Zhe Jiao 1 , Xiaoli Liu 1 , Guofu Cheng 1 , Changqin Gu 1 , Xueying Hu 1 , Wanpo Zhang 1
Scientific Reports ( IF 3.8 ) Pub Date : 2020-01-27 , DOI: 10.1038/s41598-020-57737-w Xue Wang 1 , Yanchuan Li 1 , Lintao Li 1 , Zhe Jiao 1 , Xiaoli Liu 1 , Guofu Cheng 1 , Changqin Gu 1 , Xueying Hu 1 , Wanpo Zhang 1
Affiliation
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Swine pneumonia is a great threat for pig industry around the world, which is usually accompanied with neutrophils infiltration in the airway. Although interleukin-8 (CXCL8) and its receptors, CXC chemokine receptor 1 and 2 (CXCR1/2) in human have been well documented, the expression and function of CXCR1/2 is still unknown in swine. To explore the feasibility to develop new veterinary anti-inflammatory drugs targeting porcine CXCR1/2, we detected CXCR1/2 expression in swine pneumonia through Real-Time PCR and immunohistochemistry for the first time. Two porcine CXCR1/2 antagonists, CXCL8(3-72)N11R/G31P (pN11R) and CXCL8(3-72)G31P (pG31P) were prepared and their anti-inflammatory effects were evaluated using cell chemotaxis assays and animal experiments. Our data showed that CXCR1/2 expression, which was closely related to neutrophil infiltration in the lung, was significantly up-regulated in swine pneumonia. The pN11R and pG31P could effectively inhibit the directional migration of neutrophils in vitro. In vivo data also indicated that both pN11R and pG31P significantly relieved LPS-induced pneumonia in mice through decreasing the expression of TNF-α, CXCL8, and IL-1β, and inhibiting neutrophil influx into the lung. pG31P was more efficient. Our study suggested that it is possible to develop new veterinary anti-inflammatory drugs targeting porcine CXCR1/2, and pG31P is a promising candidate.
中文翻译：
猪 CXCR1/2 拮抗剂 CXCL8(3-72)G31P 可抑制 LPS 攻击小鼠的肺部炎症。
猪肺炎是全球养猪业的一大威胁，通常伴有气道中性粒细胞浸润。尽管人类中的白细胞介素8（CXCL8）及其受体、CXC趋化因子受体1和2（CXCR1/2）已被充分记录，但CXCR1/2在猪中的表达和功能仍然未知。为了探讨开发针对猪CXCR1/2的新型兽用抗炎药物的可行性，我们首次通过Real-Time PCR和免疫组化检测了猪肺炎中CXCR1/2的表达。制备了两种猪CXCR1/2拮抗剂CXCL8（3-72）N11R/G31P（pN11R）和CXCL8（3-72）G31P（pG31P），并通过细胞趋化性测定和动物实验评估了它们的抗炎作用。我们的数据显示，与肺部中性粒细胞浸润密切相关的CXCR1/2表达在猪肺炎中显着上调。pN11R和pG31P在体外能有效抑制中性粒细胞的定向迁移。体内数据还表明，pN11R 和 pG31P 通过降低 TNF-α、CXCL8 和 IL-1β 的表达并抑制中性粒细胞流入肺部，显着缓解 LPS 诱导的小鼠肺炎。pG31P 效率更高。我们的研究表明，开发针对猪CXCR1/2的新型兽用抗炎药物是可能的，而pG31P是一个有前途的候选药物。
更新日期：2020-01-27
中文翻译：
猪 CXCR1/2 拮抗剂 CXCL8(3-72)G31P 可抑制 LPS 攻击小鼠的肺部炎症。
猪肺炎是全球养猪业的一大威胁，通常伴有气道中性粒细胞浸润。尽管人类中的白细胞介素8（CXCL8）及其受体、CXC趋化因子受体1和2（CXCR1/2）已被充分记录，但CXCR1/2在猪中的表达和功能仍然未知。为了探讨开发针对猪CXCR1/2的新型兽用抗炎药物的可行性，我们首次通过Real-Time PCR和免疫组化检测了猪肺炎中CXCR1/2的表达。制备了两种猪CXCR1/2拮抗剂CXCL8（3-72）N11R/G31P（pN11R）和CXCL8（3-72）G31P（pG31P），并通过细胞趋化性测定和动物实验评估了它们的抗炎作用。我们的数据显示，与肺部中性粒细胞浸润密切相关的CXCR1/2表达在猪肺炎中显着上调。pN11R和pG31P在体外能有效抑制中性粒细胞的定向迁移。体内数据还表明，pN11R 和 pG31P 通过降低 TNF-α、CXCL8 和 IL-1β 的表达并抑制中性粒细胞流入肺部，显着缓解 LPS 诱导的小鼠肺炎。pG31P 效率更高。我们的研究表明，开发针对猪CXCR1/2的新型兽用抗炎药物是可能的，而pG31P是一个有前途的候选药物。
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