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IL-1 promotes α-epithelial Sodium Channel (α-ENaC) expression in murine lung epithelial cells: involvement of NF-κB

  • RESEARCH ARTICLE
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Journal of Cell Communication and Signaling Aims and scope

Abstract

Intra-amniotic exposure to proinflammatory cytokines such as interleukin-1 (IL-1) correlates with a decreased incidence of respiratory distress syndrome (RDS) in infants following premature birth. At birth, inadequate absorption of fluid from the fetal lung contributes to the onset RDS. Lung fluid clearance is coupled to Na+ transport via epithelial sodium channels (ENaC). In this study, we assessed the effects of IL-1 on the expression of ENaC, particularly the α-subunit which is critical for fetal lung fluid clearance at birth. Cultured mouse lung epithelial (MLE-12) cells were treated with either IL-1α or IL-1β to determine their effects on α-ENaC expression. Changes in IL-1-induced α-ENaC levels in the presence of IL-1 receptor antagonist (IL-1ra), cycloheximide, NF-κB inhibitor, and MAP kinase inhibitors were investigated. IL-1α and IL-1β independently induced a significant increase of α-ENaC mRNA and protein after 24 h compared to untreated cells. IL-1-dependent increases in α-ENaC protein were mitigated by IL-1ra and cycloheximide. IL-1 exposure induced NF-κB binding activity. Attenuation of IL-1-induced NF-κB activation by its inhibitor SN50 decreased α-ENaC protein abundance. Inhibition of ERK 1,2 MAPK significantly decreased both IL-1α and β-induced α-ENaC protein expression whereas inhibition of p38 MAPK only blocked IL-1β-induced α-ENaC protein levels. In contrast, IL-1-induced α-ENaC protein levels were unaffected by a c-Jun N-terminal kinase (JNK) inhibitor. Our results suggest that in MLE-12 cells, IL-1-induced elevation of α-ENaC is mediated via NF-κB activation and in part involves stimulation of the ERK 1,2 and p38 MAPK signaling pathways.

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Abbreviations

IL-1:

Interleukin-1

ENaC:

Epithelial Sodium Channels

NF-κB:

Nuclear Factor kappa B

MAPK:

Mitogen Activated Protein Kinases

IL-1ra:

Interleukin-1 receptor antagonist

BPD:

Bronchopulmonary Dysplasia

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Authors and Affiliations

  1. Department of Pediatrics/Division of Neonatology, University of Texas Health Science Center, 7703 Floyd Curl Drive, MSC 7812, San Antonio, TX, 78229-3900, USA

    Shamimunisa B. Mustafa, Tania F. Hernandez, Jean A. Petershack, Barbara M. Henson & Steven R. Seidner

  2. Department of Urology, University of Texas Health Science Center, 7703 Floyd Curl Drive, MSC 7812, San Antonio, TX, 78229-3900, USA

    Teresa L. Johnson-Pais & Pratap A. Kumar

Authors
  1. Shamimunisa B. Mustafa
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  2. Tania F. Hernandez
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  3. Teresa L. Johnson-Pais
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  4. Pratap A. Kumar
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  5. Jean A. Petershack
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  6. Barbara M. Henson
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  7. Steven R. Seidner
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Correspondence to Shamimunisa B. Mustafa.

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Mustafa, S.B., Hernandez, T.F., Johnson-Pais, T.L. et al. IL-1 promotes α-epithelial Sodium Channel (α-ENaC) expression in murine lung epithelial cells: involvement of NF-κB. J. Cell Commun. Signal. 14, 303–314 (2020). https://doi.org/10.1007/s12079-019-00533-7

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  • DOI: https://doi.org/10.1007/s12079-019-00533-7

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