Myeloid-epithelial cross talk coordinates synthesis of the tissue-protective cytokine leukemia inhibitory factor during pneumonia.
Am J Physiol Lung Cell Mol Physiol
; 313(3): L548-L558, 2017 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-28522567
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 epithelial-derived cytokine was dependent on NF-κB RelA in myeloid cells. Overall, our data suggest a signaling axis whereby activation of NF-κB RelA in myeloid cells promotes epithelial LIF induction during lung infections, representing a means through which these two cell types collaborate to improve tissue resilience during pneumonia.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
/
4_TD
Base de dados:
MEDLINE
Assunto principal:
Pneumonia Bacteriana
/
Células Mieloides
/
Células Epiteliais
/
Fator Inibidor de Leucemia
Limite:
Animals
Idioma:
En
Revista:
Am J Physiol Lung Cell Mol Physiol
Ano de publicação:
2017
Tipo de documento:
Article