• Rena Brauer, Lingyin Ge, Saundra Y Schlesinger, Timothy P Birkland, Ying Huang, Tanyalak Parimon, Vivian Lee, Bonnie L McKinney, John K McGuire, William C Parks, and Peter Chen.
• 1 Women's Guild Lung Institute, Cedars-Sinai Medical Center; Los Angeles, California; and.
• Am. J. Respir. Crit. Care Med. 2016 Aug 1; 194 (3): 333344333-44.

RationaleSyndecan-1 is a cell surface heparan sulfate proteoglycan primarily expressed in the lung epithelium. Because the influenza virus is tropic to the airway epithelium, we investigated the role of syndecan-1 in influenza infection.ObjectivesTo determine the mechanism by which syndecan-1 regulates the lung mucosal response to influenza infection.MethodsWild-type (WT) and Sdc1(-/-) mice were infected with a H1N1 virus (PR8) as an experimental model of influenza infection. Human and murine airway epithelial cell cultures were also infected with PR8 to study the mechanism by which syndecan-1 regulates the inflammatory response.Measurement And Main ResultsWe found worsened outcomes and lung injury in Sdc1(-/-) mice compared with WT mice after influenza infection. Our data demonstrated that syndecan-1 suppresses bronchial epithelial apoptosis during influenza infection to limit widespread lung inflammation. Furthermore, we determined that syndecan-1 attenuated apoptosis by crosstalking with c-Met to potentiate its cytoprotective signals in airway epithelial cells during influenza infection.ConclusionsOur work shows that cell-associated syndecan-1 has an important role in regulating lung injury. Our findings demonstrate a novel mechanism in which cell membrane-associated syndecan-1 regulates the innate immune response to influenza infection by facilitating cytoprotective signals through c-Met signaling to limit bronchial epithelial apoptosis, thereby attenuating lung injury and inflammation.

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