Production of amphiregulin and recovery from influenza is greater in males than females

• DOI: 10.1186/s13293-018-0184-8
• Publication Date: 2018-06-14T01:15:31Z
• Authors: Meghan S. Vermillion; Rebecca L. Ursin; Denise I. T. Kuok; Landon G. vom Steeg; Nicholas Wohlgemuth; Olivia J. Hall; Ashley L. Fink; Eric Sasse; Andrew Nelson; Roland Ndeh; Sharon McGrath-Mo...; Wayne Mitzner; Michael C. W. Chan; Andrew Pekosz; Sabra L. Klein
• Keywords: Respiratory tract

Amphiregulin (AREG) is an epidermal growth factor that a significant mediator of tissue repair at mucosal sites, including in the lungs during influenza A virus (IAV) infection. Previous research illustrates males reproductive ages experience less severe disease and recover faster than females following infection with IAV. Whether differentially produce utilize AREG for pulmonary after IAV was investigated using murine models on C57BL/6 background primary mouse human epithelial cell culture systems. Following sublethal 2009 H1N1 IAV, adult female mice experienced greater morbidity inflammation acute phase as well worse function recovery males, despite having similar clearance kinetics. As compared females, expression male respiratory cells derived from donors, response to IAVs. Internalization receptor (EGFR) also mice. Areg knock-out (Areg−/−) eliminated sex differences pathogenesis, more role Deletion had no effect replication kinetics either sex. Gonadectomy treatment wild-type or Areg−/− testosterone improved outcome their placebo-treated conspecifics. Taken together, these data show elevated levels AREG, independently combination, improve resilience (i.e., damaged tissue) contribute better outcomes females.