Myeloid-epithelial cross talk coordinates synthesis of the tissue-protective cytokine leukemia inhibitory factor during pneumonia

American Journal of Physiology. Lung Cellular and Molecular Physiology
Katrina E TraberLee J Quinton

Abstract

In bacterial pneumonia, lung damage resulting from epithelial cell injury is a major contributor to the severity of disease and, in some cases, can lead to long-term sequelae, especially in the setting of severe lung injury or acute respiratory distress syndrome. Leukemia inhibitory factor (LIF), a member of the IL-6 cytokine family, is a critical determinant of lung tissue protection during pneumonia, but the cellular sources of LIF and the signaling pathways leading to its production in the infected lung are not known. Here, we demonstrate that lung epithelium, specifically alveolar type II cells, is the predominant site of LIF transcript induction in pneumonic mouse lungs. Epithelial cell cultures were induced to express LIF by bacteria and by sterile bronchoalveolar lavage fluid from pneumonic mice. Reciprocal bone marrow chimera studies demonstrated that LIF deficiency in the nonhematopoietic compartment, but not LIF deficiency in hematopoietic cells, eliminated LIF induction during pneumonia. Although NF-κB RelA (p65) is essential for the expression of many cytokines during pneumonia, its targeted mutation in the lung epithelium was inconsequential for pneumonia-driven LIF induction. However, maximal expression of this ep...Continue Reading

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Citations

May 17, 2018·Physiological Reviews·Lee J QuintonJoseph P Mizgerd
Nov 9, 2018·Molecular Oral Microbiology·Jeffrey L EbersoleOctavio A Gonzalez
Aug 16, 2019·PloS One·Katrina E TraberLee J Quinton
Dec 2, 2020·Pharmacology & Therapeutics·Cen ZhangZhaohui Feng
Feb 3, 2021·Infection and Immunity·Katrina E TraberLee J Quinton

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Methods Mentioned

BETA
lavage
fluorescence-activated cell sorting
FACS
PCR
ELISAs
ELISA

Software Mentioned

GraphPad Prism

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