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ELMOD2 , a candidate gene for idiopathic pulmonary fibrosis, regulates antiviral responses
Author(s) -
Pulkkinen Ville,
Bruce Sara,
Rintahaka Johanna,
Hodgson Ulla,
Laitinen Tarja,
Alenius Harri,
Kinnula Vuokko L.,
Myllarniemi Marjukka,
Matikainen Sampsa,
Kere Juha
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-138545
Subject(s) - biology , tlr3 , interferon , idiopathic pulmonary fibrosis , gene silencing , a549 cell , pulmonary fibrosis , gene expression , immunology , cancer research , fibrosis , cell culture , microbiology and biotechnology , gene , innate immune system , immune system , toll like receptor , lung , medicine , pathology , biochemistry , genetics
ABSTRACT Viral infections and abnormal host response are thought to cause epithelial injury in idiopathic pulmonary fibrosis (IPF). To understand IPF pathogenesis, we have used overexpression cell models and expression microarrays to discover genes networked with ELMO domain containing 2 (ELMOD2 ) gene genetically implicated in IPF. The identified pathways were confirmed in vitro , and ELMOD2 protein expression was characterized in tissue samples. Here 303 genes were significantly altered after ELMOD2 transfec‐tion of human alveolar epithelial A549 cell line. The enriched pathways were interferon induction, viral response, antigen processing and presentation, and I‐/ nuclear factor‐κΒ signaling. ELMOD2 showed immunoreactivity in macrophages and type II alveolar epithelial cells in normal human lung. In A549 cells, forced expression of ELMOD2 increased type I and type III interferon mRNA expression, and ELMOD2specific siRNA molecules inhibited expression of these antiviral cytokines in response to Toll‐like receptor three (TLR3) activation. In human macrophages silencing of ELMOD2 inhibited TLR3‐dependent expression of type I and type III interferon genes. Influenza A virus infection decreased ELMOD2 mRNA expression in A549 cells and macrophages suggesting negative regulation in viral infections. In summary, our results show that TLR3 pathway is dependent on ELMOD2.—Pulkkinen, V., Bruce, S., Rintahaka, J., Hodgson, U., Laitinen, T., Alenius, H., Kinnula, V. L., Myllarniemi, M., Matikainen, S., Kere, J. ELMOD2 , a candidate gene for idiopathic pulmonary fibrosis, regulates antiviral responses. FASEB J. 24, 1167–1177 (2010). www.fasebj.org