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Interleukin-11 signaling underlies fibrosis, parenchymal dysfunction, and chronic inflammation of the airway.
Ng, Benjamin; Cook, Stuart A; Schafer, Sebastian.
  • Ng B; National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore, Singapore.
  • Cook SA; Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore, Singapore.
  • Schafer S; National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore, Singapore.
Exp Mol Med ; 52(12): 1871-1878, 2020 12.
Article in English | MEDLINE | ID: covidwho-1012677
ABSTRACT
Interleukin (IL)-11 evolved as part of the innate immune response. In the human lung, IL-11 upregulation has been associated with viral infections and a range of fibroinflammatory diseases, including idiopathic pulmonary fibrosis. Transforming growth factor-beta (TGFß) and other disease factors can initiate an autocrine loop of IL-11 signaling in pulmonary fibroblasts, which, in a largely ERK-dependent manner, triggers the translation of profibrotic proteins. Lung epithelial cells also express the IL-11 receptor and transition into a mesenchymal-like state in response to IL-11 exposure. In mice, therapeutic targeting of IL-11 with antibodies can arrest and reverse bleomycin-induced pulmonary fibrosis and inflammation. Intriguingly, fibroblast-specific blockade of IL-11 signaling has anti-inflammatory effects, which suggests that lung inflammation is sustained, in part, through IL-11 activity in the stroma. Proinflammatory fibroblasts and their interaction with the damaged epithelium may represent an important but overlooked driver of lung disease. Initially thought of as a protective cytokine, IL-11 is now increasingly recognized as an important determinant of lung fibrosis, inflammation, and epithelial dysfunction.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Tract Diseases / Signal Transduction / Interleukin-11 / Inflammation Type of study: Diagnostic study / Prognostic study Limits: Animals / Humans Language: English Journal: Exp Mol Med Journal subject: Molecular Biology / Biochemistry Year: 2020 Document Type: Article Affiliation country: S12276-020-00531-5

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Tract Diseases / Signal Transduction / Interleukin-11 / Inflammation Type of study: Diagnostic study / Prognostic study Limits: Animals / Humans Language: English Journal: Exp Mol Med Journal subject: Molecular Biology / Biochemistry Year: 2020 Document Type: Article Affiliation country: S12276-020-00531-5