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This study sought to investigate the responsiveness of human lung epithelial cells to the TNF family molecules LIGHT and lymphotoxin \u03b1\u03b2 (LT\u03b1\u03b2). Bronchial and alveolar epithelial cell lines, and primary human bronchial epithelial cells, were stimulated with LIGHT and LT\u03b1\u03b2, and expression of inflammatory cytokines and chemokines and markers of epithelial-mesenchymal transition and fibrosis\/remodeling was measured. LT\u03b2 receptor, the receptor shared by LIGHT and LT\u03b1\u03b2, was constitutively expressed on all epithelial cells. Correspondingly, LIGHT and LT\u03b1\u03b2 strongly induced a limited but highly distinct set of inflammatory genes in all epithelial cells tested, namely the adhesion molecules ICAM-1 and VCAM-1; the chemokines CCL5, CCL20, CXCL1, CXCL3, CXCL5, and CXCL11; the cytokines IL-6, activin A and GM-CSF; and metalloproteinases matrix metalloproteinase-9 and a disintegrin and metalloproteinase domain-8. Importantly, induction of the majority of these inflammatory molecules was insensitive to the suppressive effects of the corticosteroid budesonide. LIGHT and LT\u03b1\u03b2 also moderately downregulated E-cadherin, a protein associated with maintaining epithelial integrity, but did not significantly drive production of extracellular matrix proteins or \u03b1-smooth muscle actin. Thus, LIGHT and LT\u03b1\u03b2 induce a distinct steroid-resistant inflammatory signature in airway epithelial cells via constitutively expressed LT\u03b2 receptor. These findings support our prior murine studies that suggested the receptors for LIGHT and LT\u03b1\u03b2 contribute to development of lung inflammation characteristic of asthma and idiopathic pulmonary fibrosis.<\/jats:p>","DOI":"10.4049\/jimmunol.1500356","type":"journal-article","created":{"date-parts":[[2015,7,25]],"date-time":"2015-07-25T03:05:08Z","timestamp":1437793508000},"page":"2429-2441","source":"Crossref","is-referenced-by-count":23,"title":["The TNF Family Molecules LIGHT and Lymphotoxin \u03b1\u03b2 Induce a Distinct Steroid-Resistant Inflammatory Phenotype in Human Lung Epithelial Cells"],"prefix":"10.1093","volume":"195","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9785-5272","authenticated-orcid":false,"given":"Ricardo","family":"da Silva Antunes","sequence":"first","affiliation":[{"name":"Division of Immune Regulation, La Jolla Institute for Allergy and Immunology , La Jolla, CA 92037"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Madge","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, Immunology Discovery Research , Spring House, PA 19002"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pejman","family":"Soroosh","sequence":"additional","affiliation":[{"name":"Janssen Research and Development , San Diego, CA 92121"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel","family":"Tocker","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, Immunology Discovery Research , Spring House, PA 19002"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Croft","sequence":"additional","affiliation":[{"name":"Division of Immune Regulation, La Jolla Institute for Allergy and Immunology , La Jolla, CA 92037"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,9,1]]},"reference":[{"key":"2025030704071446400_r1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1146\/annurev.iy.12.040194.001455","article-title":"Immunological aspects of allergic asthma","volume":"12","author":"Bochner","year":"1994","journal-title":"Annu. 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