IL-33 Mediates Inflammatory Responses in Human Lung Tissue Cells

Abstract

IL-33 is a member of the IL-1 family and mediates its biological effects via the ST2 receptor, which is selectively expressed on Th2 cells and mast cells. Although polymorphic variation in ST2 is strongly associated with asthma, it is currently unclear whether IL-33 acts directly on lung tissue cells at sites of airway remodeling. Therefore, we aimed to identify the IL-33–responsive cells among primary human lung tissue cells. ST2 mRNA was expressed in both endothelial and epithelial cells but not in fibroblasts or smooth muscle cells. Correspondingly, IL-33 promoted IL-8 production by both endothelial and epithelial cells but not by fibroblasts or smooth muscle cells. Transfection of ST2 small interference RNA into both endothelial and epithelial cells significantly reduced the IL-33–dependent upregulation of IL-8, suggesting that IL-33–mediated responses in these cells occur via the ST2 receptor. Importantly, Th2 cytokines, such as IL-4, further enhanced ST2 expression and function in both endothelial and epithelial cells. The IL-33–mediated production of IL-8 by epithelial cells was almost completely suppressed by corticosteroid treatment. In contrast, the effect of corticosteroid treatment on the IL-33–mediated responses of endothelial cells was only partial. IL-33 induced activation of both ERK and p38 MAPK in endothelial cells but only ERK in epithelial cells. p38 MAPK was required for the IL-33–mediated responses of endothelial cells, whereas ERK was required for IL-33–mediated IL-8 production by epithelial cells. Taken together, these findings suggest that IL-33–mediated inflammatory responses of lung tissue cells may be involved in the chronic allergic inflammation of the asthmatic airway.

Diagnostic Value of 25-Hydroxyvitamin D Level and New Cytokines in Neonatal Sepsis

“…Besides infectious diseases, ST2/IL-33 system is associated strongly with other infammatory diseases; Beltran et al showed significantly higher ST2/IL-33 values in patients with inflammatory bowel disease than in control group (32). Yagami et al showed that the IL-33/ST2 signaling pathway activates the production of IL-8 by epithelial cells and thereby it is related to chronic allergic inflammation of the asthmatic airways (33). We found in this study higher IL-33 and ST2 levels in group 1 than in groups 2 and 3 which is positively correlated with C-reactive protein, TNF-a and Interleukin-6.…”

The Immune-Modulating Cytokine and Endogenous Alarmin Interleukin-33 Is Upregulated in Skin Exposed to Inflammatory UVB Radiation

“…62 More recently, IL-33 was shown to induce extracellular signal-regulated kinase (ERK) expression in lung epithelial cells. 63 UVB activation of ERK not only induces proliferation of human keratinocytes, 64 it promotes keratinocyte survival by down-regulating the tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10). 65 These previous studies suggest that IL-33 may provide a growth advantage to UV-induced epithelial-derived tumor cells.…”

Anti‐inflammatory effects of high‐dose IgG on TNF‐α‐activated human coronary artery endothelial cells

“…Previously, we demonstrated that dexamethasone treatment only weakly attenuated TNF-α-induced GRO-α and IL-8 production by human pulmonary microvascular endothelial cells [35]. In observations to date, corticosteroids have been much less effective on vascular endothelial cells than on other tissue cells such as epithelial cells [35][36][37][38]. These findings correspond to the clinical fact that while corticosteroids are the most commonly used anti-inflammatory drugs for treating various inflammatory diseases, their role in the treatment of KD remains controversial [39].…”