Alveolar Epithelial STAT3, IL-6 Family Cytokines, and Host Defense during Escherichia coli Pneumonia

• DOI: 10.1165/rcmb.2007-0365oc
• Publication Date: 2008-01-11T02:18:58Z
• Authors: Lee J. Quinton; Matthew R. Jones; Bryanne E. Robson; Benjamin T. Simms; Jeffrey A. Whitsett; Joseph P. Mizgerd
• Keywords: Inflammation; STAT3 Transcription Factor; Vascular Endothelial Growth Factor A; 0301 basic medicine; Interleukin-6; Epithelial Cells; Mice, Transgenic; Cell Line; 3. Good health; Mice, Inbred C57BL; Pulmonary Alveoli; Mice; 03 medical and health sciences; Pneumonia, Bacterial; Animals; Cytokines; Humans; Chemokines; Lung; Escherichia coli Infections

While signal transducer and activator of transcription (STAT) 3 signaling has been linked to multiple pathways influencing immune function cell survival, the direct influence this factor on innate immunity tissue homeostasis during pneumonia is unknown. Human patients with dominant-negative mutations in Stat3 gene develop recurrent pneumonias, suggesting a role for STAT3 pulmonary host defense. We hypothesized that alveolar epithelial activated by IL-6 family cytokines required effective responses gram-negative bacterial pneumonia. phosphorylation was increased pneumonic mouse lungs murine lung (MLE)-15 cells stimulated bronchoalveolar lavage fluid (BALF) through 48 hours Escherichia coli Mice lacking active (Stat3(Delta/Delta)) had fewer neutrophils more viable bacteria than control mice early after intratracheal E. coli. By infection, however, injury Stat3(Delta/Delta) mice. Bacteria were cleared from both genotypes, albeit slowly Of measured infected C57BL/6 mice, IL-6, oncostatin M, leukemia inhibitory (LIF), IL-11 significantly elevated. Neutralization studies demonstrated LIF mediated BALF-induced activation MLE-15 cells. Together, these results indicate pneumonia, select members activate STAT3, which functions promote neutrophil recruitment limit infection injury.