Doxycycline exerts multiple anti-allergy effects to attenuate murine allergic conjunctivitis and systemic anaphylaxis.
Doxycycline exerts multiple anti-allergy effects to attenuate murine allergic conjunctivitis and systemic anaphylaxis.
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DOI：
10.1016/j.bcp.2014.08.001
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发表时间：
2014-10
影响因子：
5.8
通讯作者：
W. Su;Qian Wan;Longhui Han;Jingwen Huang;Xiaoqing Chen;Guihua Chen;S. Zheng;D. Liang
中科院分区：
文献类型：
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作者：
W. Su;Qian Wan;Longhui Han;Jingwen Huang;Xiaoqing Chen;Guihua Chen;S. Zheng;D. Liang
变态反应性疾病，影响高达20-30%的世界人口，仍然是变态反应学家的治疗挑战。四环素类抗生素具有多种非抗生素性质，已成功应用于多种疾病。然而，它们在过敏性结膜炎和过敏反应中的作用及其潜在的抗过敏机制仍然难以捉摸。本文报道多西环素能显著降低小鼠B细胞IgE的释放和IgE依赖性激活的肥大细胞（MC）的脱颗粒及炎性细胞因子的产生。此外，多西环素治疗显着抑制组胺诱导的血管高通透性在体外。多西环素对B细胞、MC和组胺的抑制机制可能是通过调节PI 3 K/Akt通路而实现的，我们的研究结果表明，多西环素治疗可显著减轻实验性过敏性结膜炎（EAC）小鼠模型的临床症状，显著减少炎性细胞频率、IgE产生、组胺释放以及TNF-α和IL-4产生。使用MC依赖性被动全身过敏反应（PSA）的小鼠模型，我们进一步证实了多西环素的抗过敏作用和多西环素介导的对MC的抑制作用。此外，我们的研究结果表明，多西环素显着减弱组胺诱导的全身过敏样反应（HISA），并显着下调PI 3 K/Akt/eNOS/VE-cadherin途径。当给予Akt激活剂SC 79时，EAC、PSA和HISA期间强力霉素介导的抗过敏作用被废除。这些结果表明，强力霉素抑制B细胞，MC和组胺功能，并减轻实验性过敏性结膜炎和全身过敏反应，可能通过调节PI 3 K/Akt途径。
Allergic diseases, which affect up to 20–30% of the world population, are still therapeutic challenge for allergists. Tetracyclines, which belong to an antibiotic drug family that possesses a striking variety of non-antibiotic properties, have been successfully applied to a wide range of diseases. However, their roles in allergic conjunctivitis and anaphylaxis and their underlying anti-allergy mechanisms remain elusive. Here, we reported that treatment with doxycycline significantly reduced IgE release from mouse B cells and the degranulation and inflammatory cytokines production of mouse mast cells (MCs) activated by IgE-dependent way. Furthermore, doxycycline treatment significantly inhibited histamine-induced vascular hyperpermeabilityin vitro. Mechanistically, the doxycycline-mediated inhibition of B cells, MCs and histamine may occurviamodulation of the PI3K/Akt pathway.In vivo, our results demonstrated that treatment with doxycycline significantly attenuated clinical symptoms of mouse models of experimental allergic conjunctivitis (EAC) with a significant decrease in inflammatory cell frequency, IgE production, histamine release, and a decrease in TNF-α and IL-4 production. Using mouse models of MCs-dependent passive systemic anaphylaxis (PSA), we further confirmed anti-allergy effects of doxycycline and doxycycline-mediated inhibitory effects on MCs. Furthermore, our results showed that doxycycline significantly attenuate histamine-induced systemic anaphylaxis-like reaction (HISA) with a significantly downregulation of PI3K/Akt/eNOS/VE-cadherin pathway. The doxycycline-mediated anti-allergy effects during EAC, PSA and HISA were abrogated when an Akt activator, SC79, was administered. These findings suggest that doxycycline inhibits B cell, MC and histamine function and attenuates experimental allergic conjunctivitis and systemic anaphylaxis by possible modulating the PI3K/Akt pathway.