IL-33 mediated amplification of allergic response in human mast cells

Abstract

Context: 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.Objective: Present study aims to explore the IL-33 mediated effects of histamine induced allergic inflammation in human mast cells.Materials and methods: 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.Results: 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.Conclusions: 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.