biostudies-literatureLiu MJNCATS NIH HHSNHLBI NIH HHSe94934https://www.ebi.ac.uk/biostudies/studies/S-EPMC3986341biostudies-literatureUnknown9(4)Sepsis rapidly activates the host inflammatory response and acute phase response. Severe sepsis, complicated by multiple organ failure, is associated with overwhelming inflammation and high mortality. We previously observed that zinc (Zn) deficiency significantly increases mortality in a mouse model of polymicrobial sepsis due to over-activation of the inflammatory response. In order to identify potential mechanisms that account for Zn-responsive effects, we generated whole exome expression profiles from the lung tissue of septic mice that were maintained on Zn modified diets. Based on systems analysis, we observed that Zn deficiency enhances the acute phase response and particularly the JAK-STAT3 pathway, resulting in increased serum amyloid A production. In vitro studies of primary hepatPloS oneZinc regulates the acute phase response and serum amyloid A production in response to sepsis through JAK-STAT3 signaling.PMC3986341R01 HL086981-01UL1 TR001070R01 HL086981Knoell DLBurris DLYu LLiu MJTridandapani SBao SNapolitano JRfalseZinc regulates the acute phase response and serum amyloid A production in response to sepsis through JAK-STAT3 signaling.Sepsis rapidly activates the host inflammatory response and acute phase response. Severe sepsis, complicated by multiple organ failure, is associated with overwhelming inflammation and high mortality. We previously observed that zinc (Zn) deficiency significantly increases mortality in a mouse model of polymicrobial sepsis due to over-activation of the inflammatory response. In order to identify potential mechanisms that account for Zn-responsive effects, we generated whole exome expression profiles from the lung tissue of septic mice that were maintained on Zn modified diets. Based on systems analysis, we observed that Zn deficiency enhances the acute phase response and particularly the JAK-STAT3 pathway, resulting in increased serum amyloid A production. In vitro studies of primary hepat2014-01-01T00:00:00Z20142026-04-07T16:25:12.966Z2019-03-26T23:24:25ZS-EPMC39863412473291110.1371/journal.pone.0094934