{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T10:13:37Z","timestamp":1781259217228,"version":"3.54.1"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,1,18]],"date-time":"2017-01-18T00:00:00Z","timestamp":1484697600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>The epithelial and endothelial barriers of the airway mucosa are critical for regulation of tissue homeostasis and protection against pathogens or other tissue damaging agents. In response to a viral infection, epithelial cells must signal to the endothelium to initiate immune cell recruitment. This is a highly temporal regulated process; however, the mechanisms of this cross\u2010talk are not fully understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a close\u2010contact co\u2010culture model of human airway epithelial and endothelial cells, cellular crosstalk was analyzed using transepithelial electrical resistance (TER) measurements, immunofluorescence, electron microscopy, and ELISA. Viral infections were simulated by exposing airway epithelial cells apically to double\u2010stranded RNA (Poly(I:C)). Using a microfluidic culture system, the temporal release of mediators was analyzed in the co\u2010culture model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Within 4\u2009h of challenge, double\u2010stranded RNA induced the release of TNF\u2010\u03b1 by epithelial cells. This activated endothelial cells by triggering the release of the chemoattractant CX<jats:sub>3<\/jats:sub>CL1 (fractalkine) by 8\u2009h post\u2010challenge and expression of adhesion molecules E\u2010selectin and ICAM\u20101. These responses were significantly reduced by neutralising TNF\u2010\u03b1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>By facilitating kinetic profiling, the microfluidic co\u2010culture system has enabled identification of a key signaling mechanism between the epithelial and endothelial barriers. Better understanding of cell\u2013cell cross\u2010talk and its regulatory mechanisms has the potential to identify new therapeutic strategies to control airway inflammation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.139","type":"journal-article","created":{"date-parts":[[2017,1,19]],"date-time":"2017-01-19T01:50:27Z","timestamp":1484790627000},"page":"45-56","source":"Crossref","is-referenced-by-count":45,"title":["Cellular crosstalk between airway epithelial and endothelial cells regulates barrier functions during exposure to double\u2010stranded RNA"],"prefix":"10.1002","volume":"5","author":[{"given":"Cornelia","family":"Blume","sequence":"first","affiliation":[{"name":"Academic Unit of Clinical and Experimental Sciences Faculty of Medicine University of Southampton Southampton United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Reale","sequence":"additional","affiliation":[{"name":"Electronics and Computer Sciences Faculty of Physical and Applied Sciences University of Southampton Southampton United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Held","sequence":"additional","affiliation":[{"name":"Electronics and Computer Sciences Faculty of Physical and Applied Sciences University of Southampton Southampton United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Loxham","sequence":"additional","affiliation":[{"name":"Academic Unit of Clinical and Experimental Sciences Faculty of Medicine University of Southampton Southampton United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy M.","family":"Millar","sequence":"additional","affiliation":[{"name":"Academic Unit of Clinical and Experimental Sciences Faculty of Medicine University of Southampton Southampton United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane E.","family":"Collins","sequence":"additional","affiliation":[{"name":"Academic Unit of Clinical and Experimental Sciences Faculty of Medicine University of Southampton Southampton United Kingdom"},{"name":"Institute for Life Sciences University of Southampton Southampton United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily J.","family":"Swindle","sequence":"additional","affiliation":[{"name":"Academic Unit of Clinical and Experimental Sciences Faculty of Medicine University of Southampton Southampton United Kingdom"},{"name":"Institute for Life Sciences University of Southampton Southampton United Kingdom"},{"name":"National Institute for Health Research Southampton Respiratory Biomedical Research Unit University Hospital Southampton Southampton United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hywel","family":"Morgan","sequence":"additional","affiliation":[{"name":"Electronics and Computer Sciences Faculty of Physical and Applied Sciences University of Southampton Southampton United Kingdom"},{"name":"Institute for Life Sciences University of Southampton Southampton United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna E.","family":"Davies","sequence":"additional","affiliation":[{"name":"Academic Unit of Clinical and Experimental Sciences Faculty of Medicine University of Southampton Southampton United Kingdom"},{"name":"Institute for Life Sciences University of Southampton Southampton United Kingdom"},{"name":"National Institute for Health Research Southampton Respiratory Biomedical Research Unit University Hospital Southampton Southampton United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,1,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(78)90104-4"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12309"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201407-304AW"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2012.12.014"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2012.08.006"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055311"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/801214"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743-8977-8-6"},{"key":"e_1_2_7_10_1","first-page":"1","article-title":"Small airway epithelial cells exposure to printer\u2010emitted engineered nanoparticles induces cellular effects on human microvascular endothelial cells in an alveolar\u2010capillary co\u2010culture model","volume":"2014","author":"Sisler J. 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