Activation of Hepatic STAT3 Maintains Pulmonary Defense during Endotoxemia

• DOI: 10.1128/iai.00464-15
• Publication Date: 2015-07-28T01:01:53Z
• Authors: Kristie L. Hilliard; Eri Allen; Katrina E. Traber; Yuri Kim; Gregory A. Wasserman; Matthew R. Jones; Joseph P. Mizgerd; Lee J. Quinton
• Keywords: Ex vivo

Pneumonia and infection-induced sepsis are worldwide public health concerns. Both pathologies elicit systemic inflammation induce a robust acute-phase response (APR). Although APR activation is well regarded as hallmark of infection, the direct contributions liver to pulmonary defense during remain unclear. By targeting STAT3-dependent changes in liver, we evaluated role STAT3 activity promoting host context pneumonia. We employed two-hit endotoxemia/pneumonia model, whereby administration 18 h intraperitoneal lipopolysaccharide (LPS; 5 mg/kg body weight) was followed by intratracheal Escherichia coli (10(6) CFU) wild-type mice or those lacking hepatocyte (hepSTAT3(-/-)). alone (without endotoxemia) effectively controlled absence STAT3. Following endotoxemia pneumonia, however, hepSTAT3(-/-) mice, with significantly reduced levels circulating airspace proteins, exhibited elevated lung blood bacterial burdens mortality. These data suggested that responses necessary promote defense. While neither recruited neutrophils nor injury altered endotoxemic alveolar macrophage reactive oxygen species generation decreased. Additionally, bronchoalveolar lavage fluid from this group allowed greater growth ex vivo. results suggest hepatic promotes both cellular humoral defenses. Taken together, induction gene expression programs essential countering deleterious consequences on pneumonia susceptibility.