Apoptosis signal-regulating kinase-1 promotes inflammasome priming in macrophages

Camille N. Immanuel, Bin Teng, Brittany Dong, Elizabeth M. Gordon, Joseph A. Kennedy, Charlean Luellen, Andreas Schwingshackl, Stephania A. Cormier, Elizabeth Fitzpatrick, Christopher M. Waters

Research output: Contribution to journalArticle

Abstract

previously showed that mice deficient in apo-ptosis signal-regulating kinase-1 (ASK1) were partially protected against ventilator-induced lung injury. Because ASK1 can promote both cell death and inflammation, we hypothesized that ASK1 activation regulates inflammasome-mediated inflammation. Mice deficient in ASK1 expression (ASK1 +/+ ) exhibited significantly less inflammation and lung injury (as measured by neutrophil infiltration, IL-6, and IL-1β) in response to treatment with inhaled lipopolysaccharide (LPS) compared with wild-type (WT) mice. To determine whether this proinflammatory response was mediated by ASK1, we investigated inflammasome-mediated responses to LPS in primary macrophages and bone marrow-derived macrophages (BMDMs) from WT and ASK1 +/+ mice, as well as the mouse alveolar macrophage cell line MH-S. Cells were treated with LPS alone for priming or LPS followed by ATP for activation. When macrophages were stimulated with LPS followed by ATP to activate the inflammasome, we found a significant increase in secreted IL-1β from WT cells compared with ASK1-deficient cells. LPS priming stimulated an increase in NOD-like receptor 3 (NLRP3) and pro-IL-1β in WT BMDMs, but expression of NLRP3 was significantly decreased in ASK1 +/+ BMDMs. Subsequent ATP treatment stimulated an increase in cleaved caspase-1 and IL-1β in WT BMDMs compared with ASK1 +/+ BMDMs. Similarly, treatment of MH-S cells with LPS + ATP caused an increase in both cleaved caspase-1 and IL-1β that was diminished by the ASK-1 inhibitor NQDI1. These results demonstrate, for the first time, that ASK1 promotes inflammasome priming.

Original languageEnglish (US)
Pages (from-to)L418-L427
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume316
Issue number3
DOIs
StatePublished - Mar 1 2019

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MAP Kinase Kinase Kinase 5
Inflammasomes
Phosphotransferases
Macrophages
Lipopolysaccharides
Interleukin-1
Adenosine Triphosphate
Caspase 1
Inflammation
Ventilator-Induced Lung Injury
Alveolar Epithelial Cells
Neutrophil Infiltration
Alveolar Macrophages
Lung Injury

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Immanuel, C. N., Teng, B., Dong, B., Gordon, E. M., Kennedy, J. A., Luellen, C., ... Waters, C. M. (2019). Apoptosis signal-regulating kinase-1 promotes inflammasome priming in macrophages. American Journal of Physiology - Lung Cellular and Molecular Physiology, 316(3), L418-L427. https://doi.org/10.1152/ajplung.00199.2018

Apoptosis signal-regulating kinase-1 promotes inflammasome priming in macrophages. / Immanuel, Camille N.; Teng, Bin; Dong, Brittany; Gordon, Elizabeth M.; Kennedy, Joseph A.; Luellen, Charlean; Schwingshackl, Andreas; Cormier, Stephania A.; Fitzpatrick, Elizabeth; Waters, Christopher M.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 316, No. 3, 01.03.2019, p. L418-L427.

Research output: Contribution to journalArticle

Immanuel, CN, Teng, B, Dong, B, Gordon, EM, Kennedy, JA, Luellen, C, Schwingshackl, A, Cormier, SA, Fitzpatrick, E & Waters, CM 2019, 'Apoptosis signal-regulating kinase-1 promotes inflammasome priming in macrophages' American Journal of Physiology - Lung Cellular and Molecular Physiology, vol. 316, no. 3, pp. L418-L427. https://doi.org/10.1152/ajplung.00199.2018
Immanuel, Camille N. ; Teng, Bin ; Dong, Brittany ; Gordon, Elizabeth M. ; Kennedy, Joseph A. ; Luellen, Charlean ; Schwingshackl, Andreas ; Cormier, Stephania A. ; Fitzpatrick, Elizabeth ; Waters, Christopher M. / Apoptosis signal-regulating kinase-1 promotes inflammasome priming in macrophages. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2019 ; Vol. 316, No. 3. pp. L418-L427.
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