酸离子敏感通道1a(acid-sensing ion channel 1a,ASIC1a)属于氨氯敏感配体门控离子通道,在中枢和外周神经系统中广泛分布及表达。在生理环境下,细胞通过H^+的多种转运方式维持细胞外和细胞内的pH值并相对稳定在7.0~7.5左右。在一些病理...酸离子敏感通道1a(acid-sensing ion channel 1a,ASIC1a)属于氨氯敏感配体门控离子通道,在中枢和外周神经系统中广泛分布及表达。在生理环境下,细胞通过H^+的多种转运方式维持细胞外和细胞内的pH值并相对稳定在7.0~7.5左右。在一些病理条件如过敏性哮喘、肾炎、关节炎、肠炎、急性肺损伤等炎症性疾病的发生过程中,由于组织的无氧糖酵解产生乳酸和ATP水解的H^+积聚,导致组织酸化及体液pH值急剧下降至4.0~6.0左右,而进一步激活的ASIC1a可引起炎症性疾病病情急剧恶化。近年来,靶向ASIC1a可能是一种潜在的治疗策略,本文就ASIC1a在炎症性疾病中的作用做简要综述,探讨ASIC1a在炎症性疾病中的研究进展。展开更多
Macrophages show significant heterogeneity in function and phenotype, which could shift into different populations of cells in response to exposure to various micro-environmental signals. These changes, also termed as...Macrophages show significant heterogeneity in function and phenotype, which could shift into different populations of cells in response to exposure to various micro-environmental signals. These changes, also termed as macrophage polarization, of which play an important role in the pathogenesis of many diseases. Numerous studies have proved that Hesperidin(HDN), a traditional Chinese medicine, extracted from fruit peels of the genus citrus, play key roles in anti-inflammation, anti-tumor, anti-oxidant and so on. However, the role of HDN in macrophage polarization has never been reported. Additional, because of its poor water solubility and bioavailability. Our laboratory had synthesized many hesperidin derivatives. Among them, hesperidin derivatives-12(HDND-12) has better water solubility and bioavailability. So, we evaluated the role of HDND-12 in macrophage polarization in the present study. The results showed that the expression of Arginase-1(Arg-1), interleukin-10(IL-10), transforming growth factor β(TGF-β) were up-regulated by HDND-12, whereas the expression of inducible Nitric Oxide Synthase(iNOS) was down-regulated in LPS-and IFN-γ-treated(M1) RAW264.7 cells. Moreover, the expression of p-JAK2 and p-STAT3 were significantly decreased after stimulation with HDND-12 in M1-like macrophages. More importantly, when we taken AG490(inhibitor of JAK2/STAT3 signaling), the protein levels of iNOS were significantly reduced in AG490 stimulation group compare with control in LPS, IFN-γ and HDND-12 stimulation cells. Taken together, these findings indicated that HDND-12 could prevent polarization toward M1-like macrophages, at least in part, through modulating JAK2/STAT3 pathway.展开更多
基金grants from the National Natural Science Foundation of China (No.81570623)Science Funds for Distinguished Young Scholars of Anhui Province, China (No.1608085J07)。
文摘酸离子敏感通道1a(acid-sensing ion channel 1a,ASIC1a)属于氨氯敏感配体门控离子通道,在中枢和外周神经系统中广泛分布及表达。在生理环境下,细胞通过H^+的多种转运方式维持细胞外和细胞内的pH值并相对稳定在7.0~7.5左右。在一些病理条件如过敏性哮喘、肾炎、关节炎、肠炎、急性肺损伤等炎症性疾病的发生过程中,由于组织的无氧糖酵解产生乳酸和ATP水解的H^+积聚,导致组织酸化及体液pH值急剧下降至4.0~6.0左右,而进一步激活的ASIC1a可引起炎症性疾病病情急剧恶化。近年来,靶向ASIC1a可能是一种潜在的治疗策略,本文就ASIC1a在炎症性疾病中的作用做简要综述,探讨ASIC1a在炎症性疾病中的研究进展。
基金supported by the Key Fund Project of Anhui Education Department(No.KJ2016A364)National Natural Science Foundation of China(No.81473268)
文摘Macrophages show significant heterogeneity in function and phenotype, which could shift into different populations of cells in response to exposure to various micro-environmental signals. These changes, also termed as macrophage polarization, of which play an important role in the pathogenesis of many diseases. Numerous studies have proved that Hesperidin(HDN), a traditional Chinese medicine, extracted from fruit peels of the genus citrus, play key roles in anti-inflammation, anti-tumor, anti-oxidant and so on. However, the role of HDN in macrophage polarization has never been reported. Additional, because of its poor water solubility and bioavailability. Our laboratory had synthesized many hesperidin derivatives. Among them, hesperidin derivatives-12(HDND-12) has better water solubility and bioavailability. So, we evaluated the role of HDND-12 in macrophage polarization in the present study. The results showed that the expression of Arginase-1(Arg-1), interleukin-10(IL-10), transforming growth factor β(TGF-β) were up-regulated by HDND-12, whereas the expression of inducible Nitric Oxide Synthase(iNOS) was down-regulated in LPS-and IFN-γ-treated(M1) RAW264.7 cells. Moreover, the expression of p-JAK2 and p-STAT3 were significantly decreased after stimulation with HDND-12 in M1-like macrophages. More importantly, when we taken AG490(inhibitor of JAK2/STAT3 signaling), the protein levels of iNOS were significantly reduced in AG490 stimulation group compare with control in LPS, IFN-γ and HDND-12 stimulation cells. Taken together, these findings indicated that HDND-12 could prevent polarization toward M1-like macrophages, at least in part, through modulating JAK2/STAT3 pathway.
