Interleukin-33 and its Receptor in Pulmonary Inflammatory Diseases

Abstract

Interleukin-33 (IL-33) is a member of the IL-1 cytokine family. It modulates immune responses and biological functions through binding to its membrane receptor, ST2L. ST2L is a member of the Toll-like/IL-1 (TIR)–receptor superfamily, and its isoform, soluble ST2 (sST2), functions as an inhibitor of the IL-33/ST2L pathway. Levels of IL-33 and sST2 in serum and bronchoalveolar lavage fluid (BAL) are known biomarkers for a variety of disorders such as heart failure, non-small-cell lung cancer, and pulmonary inflammatory diseases. IL-33 also exists in the nuclei, and nuclear IL-33 seems to regulate cytokine gene expression. In this review, we focus on the role of IL-33/ST2 in the pathogenesis of pulmonary inflammatory diseases including asthma, chronic obstructive pulmonary disease (COPD), and lung injury.

IL-33-HIF1α Axis in Hypoxic Pulmonary Hypertension

“…The present work by Liu et al complements prior reports on IL-33/ST2 in inflammation and remodeling processes [ [7] , [8] , [9] ], while supporting the clinical relevance of these findings by observing similar molecules upregulated in the structural endothelial cells of blood vessels of hypoxic patients. The requirement of ST2 receptor for the effect of HIF1α on VEGF as shown by Liu et al is interesting and points to a novel insight into HIF1α regulation.…”

IL-33 Initiates Vascular Remodelling in Hypoxic Pulmonary Hypertension by up-Regulating HIF-1α and VEGF Expression in Vascular Endothelial Cells

“…Although IL-33 has now been implicated in the pathogenesis of many lung inflammatory and remodelling processes [ [21] , [22] , [23] ], its possible role in the pathogenesis of HPH per se remains unclear. Our observation that the expression of IL-33 and its receptor ST2 is up regulated in pulmonary arterial endothelial cells in sections of lung tissue obtained from murine model of HPH and from patients with HPH impelled us further to explore the potential roles of IL-33/ST2/HIF-1α/VEGF signalling pathways in the pathogenesis of this phenomenon using in vivo and in vitro experiments.…”

COVID-19: In the Eye of the Cytokine Storm

“…In allergic asthma, epithelial cells respond to the presence of the allergen by producing cytokines such as IL-25 and IL-33 (14). In turn, these activate the TH2 response mediated by IL-4, IL-13, and IL-5 (15). IL-4 and IL-13 are important for regulating the production of IgE and the activation of macrophages (14), while IL-5 mediates eosinophilic inflammation (15,16).…”

“…In turn, these activate the TH2 response mediated by IL-4, IL-13, and IL-5 (15). IL-4 and IL-13 are important for regulating the production of IgE and the activation of macrophages (14), while IL-5 mediates eosinophilic inflammation (15,16). COPD is a chronic inflammation of the lungs, which is usually triggered by long-term exposure to particulate matter or smoke.…”