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.

• Authors: Akiko Yagami, Kanami Orihara, Hideaki Morita, Kyoko Futamura, Noriko Hashimoto, Kenji Matsumoto, Hirohisa Saito, Akio Matsuda
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 185 Issue 10 Pg. 5743-50 (Nov 15 2010) ISSN: 1550-6606 [Electronic] United States
• PMID: 20926795 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• IL1RL1 protein, human
• IL33 protein, human
• Interleukin-1 Receptor-Like 1 Protein
• Interleukin-33
• Interleukin-8
• Interleukins
• RNA, Small Interfering
• Receptors, Cell Surface

Topics

• Asthma (metabolism)
• Blotting, Western
• Cells, Cultured
• Endothelial Cells (immunology, metabolism)
• Enzyme-Linked Immunosorbent Assay
• Epithelial Cells (immunology, metabolism)
• Fibroblasts (immunology, metabolism)
• Humans
• Inflammation (immunology, metabolism)
• Interleukin-1 Receptor-Like 1 Protein
• Interleukin-33
• Interleukin-8 (immunology, metabolism)
• Interleukins (immunology, metabolism)
• Lung (cytology, immunology, metabolism)
• Myocytes, Smooth Muscle (immunology, metabolism)
• RNA, Small Interfering
• Receptors, Cell Surface (immunology, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (immunology)
• Transfection