Parveen Shahana, Saravanan Dhivya Bharathi, Saluja Rohit, Elden Berla Thangam
Department of Biotechnology, School of Bio-Engineering, SRM Institute of Science and Technology, Chennai, India.
Department of Biochemistry, All India Institute of Medical Sciences, Bhopal, India.
J Recept Signal Transduct Res. 2019 Aug;39(4):359-367. doi: 10.1080/10799893.2019.1690515. Epub 2019 Nov 22.
IL-33 is a pro-inflammatory cytokine that is involved in the development of chronic inflammatory diseases and the initiation of allergic inflammation in response to pathogens and acts an alarmin. Present study aims to explore the IL-33 mediated effects of histamine induced allergic inflammation in human mast cells. In this study, cord blood derived CD34+ mast cells and HMC-1 cells were primed with IL-33 followed by the stimulation with histamine. We investigated the functional activation of mast cell by intracellular calcium release using calcium mobilization assay, release of granular content using degranulation assay, profiling of various inflammatory and regulatory cytokines as well as chemokines by Luminex Bioplex assay and its signaling mechanisms involved using western blot analysis. In our study, we found that the IL-33 acts as a mediator in the allergic inflammation induced by the histamine. IL-33 potentiates the release of intracellular calcium and degranulation content in human mast cells. Also, it enhances the production of Th2, Th1 cytokines and chemokines and down-regulates the production of regulatory cytokine. Furthermore, it enhanced the phosphorylation of the signaling molecules such as ERK, Akt, and NFκB in activated mast cells. Therefore, IL-33 acts as a potent activator of mast cells and it can elicit inflammatory response synergistically with histamine. Taken together, IL-33 acts as a potent mediator by inducing the inflammatory response in activated mast cells, hence increasing their responsiveness to antigens and amplifying the allergic response.
白细胞介素-33（IL-33）是一种促炎细胞因子，参与慢性炎症性疾病的发展以及对病原体的过敏性炎症的启动，并作为一种警报素发挥作用。本研究旨在探讨IL-33介导的组胺诱导的人肥大细胞过敏性炎症的影响。在本研究中，用IL-33预处理脐血来源的CD34+肥大细胞和HMC-1细胞，然后用组胺刺激。我们通过钙动员试验利用细胞内钙释放研究肥大细胞的功能激活，通过脱颗粒试验研究颗粒内容物的释放，通过Luminex Bioplex试验分析各种炎性和调节性细胞因子以及趋化因子的谱，并使用蛋白质印迹分析其涉及的信号机制。在我们的研究中，我们发现IL-33在组胺诱导的过敏性炎症中起介质作用。IL-33增强人肥大细胞内钙的释放和脱颗粒内容物的释放。此外，它增强Th2、Th1细胞因子和趋化因子的产生，并下调调节性细胞因子的产生。此外，它增强了活化肥大细胞中ERK、Akt和NFκB等信号分子的磷酸化。因此，IL-33作为肥大细胞的有效激活剂，可与组胺协同引发炎症反应。综上所述，IL-33通过在活化的肥大细胞中诱导炎症反应，从而增加其对抗原的反应性并放大过敏反应，作为一种有效的介质发挥作用。
