Abstract
Abstract The prevalence of Allergy and Asthma has been increasing over the past decade, and about 300 million people suffer from these diseases worldwide. Interleukin-33 (IL-33), an Interleukin-1 family of cytokine, binds with the IL-33 receptor (IL-33R) to elicit an array of molecular and cellular processes in immune cells. Here, we have studied the role of IL-33 in mast cell-mediated responses and its impact on allergic asthma using systems immunological methodologies. We have obtained all the microarray datasets from the Gene Expression Omnibus (GEO) related to the IL-33 treated mast cells and allergic asthma. The datasets were analyzed using Genespring GX12.6 (Agilent Technologies, USA) to classify the differentially expressed genes (P<0.05) compared to untreated controls. The ingenuity pathway analysis (Qiagen, USA) of the IL-33 triggered differentially expressed genes in mast cells have revealed that the canonical pathways such as T-helper cell differentiation, the role of macrophages, fibroblasts, endothelial cells in autoimmunity, and chemokine signaling were significantly (P<0.05) upregulated. Besides, in-depth analyses of the IL-33 induced differentially expressed genes in mast cells and allergic asthma, using the comparison analysis module in IPA, showed a significant attenuation in HCK and other related signaling networks. However, the stimulation of both Th1 and Th2 associated cytokines by IL-33 could differentially regulate allergic asthma. Thus, IL-33 is a Janus-Faced cytokine in mast cell mediated allergic responses and, hence, requires further in vitro and in vivo studies to evaluate the therapeutic importance.
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