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Myeloid Depletion of SOCS3 Enhances LPS‐Induced Acute Lung Injury through CCAAT/Enhancer Binding Protein delta Pathway
Author(s) -
Gao Hongwei,
Yan Chunguang,
Wang Ximo
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1166.9
Subject(s) - socs3 , proinflammatory cytokine , chemokine , lung , cytokine , ccaat enhancer binding proteins , chemistry , immunology , inflammation , medicine , microbiology and biotechnology , biology , signal transduction , stat3 , transcription factor , biochemistry , nuclear protein , gene
Objective SOCS3 is an important negative regulator of IL‐6‐type cytokine signaling. SOCS3 is induced in lung during LPS‐induced lung injury. The objective of this study is to test the hypothesis that SOCS3 is a critical regulator of LPS‐induced ALI. Methods We created mice lacking SOCS3 expression in macrophages and neutrophils ( LysM‐cre SOCS3 fl/fl ). We evaluated the lung inflammatory response to LPS in both LysM‐cre SOCS3 fl/fl mice and the wild type mice (SOCS3 fl/fl ). We also determined the role of CCAAT/enhancer‐binding proteins (C/EBP)β and ‐δ in LPS‐induced ALI by using C/EBPβ and ‐δ mutant mice. Results LysM‐cre SOCS3 fl/fl mice displayed significant increase of the lung permeability index (lung vascular leak of albumin), lung neutrophil accumulation (MPO activity), neutrophils and proinflammatory cytokines/chemokines in bronchial alveolar lavage (BAL) fluids compared to wild‐type mice. These phenotypes were consistent with morphological evaluation of lung, which showed enhanced inflammatory cell influx and intra‐alveolar hemorrhage. We further identify C/EBPδ, but not C/EBPβ, as a critical downstream mediator of SOCS3 in LPS‐induced ALI. Conclusions Results indicate that SOCS3 has a protective role in LPS‐induced ALI by suppressing C/EBPδ activity in the lung. Elucidating the function of SOCS3 and C/EBPδ would represent prospective targets for a new generation of drugs needed to treat ALI.