title: SOCS-1 rescues IL-1β-mediated suppression of epithelial sodium channel in mouse lung epithelial cells via ASK-1.
abstract: BACKGROUND
  Acute lung injury (ALI) is characterized by alveolar damage, increased levels of pro-inflammatory cytokines and impaired alveolar fluid clearance. Recently, we showed that the deletion of Apoptosis signal-regulating kinase 1 (ASK1) protects against hyperoxia-induced acute lung injury (HALI) by suppressing IL-1β and TNF-α. Previously, our data revealed that the suppressor of cytokine signaling-1 (SOCS-1) overexpression restores alveolar fluid clearance in HALI by inhibiting ASK-1 and suppressing IL-1β levels. Furthermore, IL-1β is known to inhibit the expression of epithelial sodium channel α-subunit (ENaC) via a p38 MAPK signaling pathway.
  
  
  OBJECTIVE
  To determine whether SOCS-1 overexpression in MLE-12 cells would protect against IL-1β-mediated depletion of αENaC by suppressing ASK-1 expression.
  
  
  METHODS
  We co-transfected MLE-12 cells with SOCS-1 overexpressing plasmid with or without IL-1β in the presence or absence of sodium channel inhibitor, amiloride. We measured potential difference, transepithelial current, resistance, and sodium uptake levels across MLE-12 cells. We studied the effect of ASK-1 depletion, as well as ASK-1 and SOCS-1 overexpression on αENaC expression.
  
  
  RESULTS
  SOCS-1 overexpression sufficiently restored transepithelial current and resistance in MLE-12 cells treated with either IL-1β or amiloride. The αENaC mRNA levels and sodium transport were increased in SOCS-1 overexpressing MLE-12 cells exposed to IL-1β. Depletion of ASK-1 in MLE-12 cells increased αENaC mRNA levels. Interestingly, SOCS-1 overexpression restored αENaC expression in MLE-12 cells in the presence of ASK-1 overexpression.
  
  
  CONCLUSIONS
  Collectively, these findings suggest that SOCS-1 may exert its protective effect by rescuing αENaC expression via suppression of ASK-1.
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Galam
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Ramani
authors.initials: R
authors.lastname: Soundararajan
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Mason
authors.initials: M
authors.lastname: Breitzig
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Ashna
authors.initials: A
authors.lastname: Rajan
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Rajashekar Reddy
authors.initials: RR
authors.lastname: Yeruva
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Czachor
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Francine
authors.initials: F
authors.lastname: Harris
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Lockey
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Narasaiah
authors.initials: N
authors.lastname: Kolliputi
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D051379:Mice; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000378:metabolism*
chemical_list: D053503:Epithelial Sodium Channels; D053583:Interleukin-1beta; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein
keywords: ASK-1; SOCS-1; edema; inflammation; lung injury