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Dendritic cell‐derived interferon‐γ‐induced protein mediates tumor necrosis factor‐α stimulation of human lung fibroblasts
Author(s) -
Liao Wupeng,
Bao Zhang,
Cheng Chang,
Mok YuKeung,
Wong W. S. Fred
Publication year - 2008
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200700954
Subject(s) - tumor necrosis factor alpha , fibroblast , thymic stromal lymphopoietin , biology , isg15 , inflammation , microbiology and biotechnology , cancer research , immunology , cell culture , biochemistry , gene , genetics , ubiquitin
Lung fibroblast plays a pivotal role in lung repair and remodeling, and also contributes to lung inflammation. The present study investigated differential protein profiling of normal human lung fibroblasts stimulated with tumor necrosis factor (TNF)‐α. Total proteins from lung fibroblasts were separated by 2‐DE, and differentially expressed proteins were identified by MALDI‐TOF MS. TNF‐α was found for the first time to alter the expression levels of myxovirus resistance protein A, interferon‐stimulated gene 15, plasminogen activator inhibitor‐2, lysyl hydroxylase 2 (isoform a), and prolyl 4‐hydroxylase (α subunit) in human lung fibroblasts. In particular, dendritic cell‐derived interferon‐γ‐induced protein (DCIP) was upregulated by TNF‐α in lung fibroblasts and its biological function is at present unknown. We found that TNF‐α‐induced DCIP expression was dependent on the transcription factor interferon regulatory factor‐1. DCIP‐selective antisense oligodeoxynucleotide inhibited the expression of TNF‐α‐responsive gene targets including vascular cell adhesion molecule‐1, intercellular adhesion molecule‐1, IL‐6, IL‐8, IP‐10, and thymic stromal lymphopoietin. In a lipopolysaccharide‐induced acute lung injury mouse model, DCIP mRNA level was elevated together with that of TNF‐α. We have demonstrated for the first time that DCIP is upregulated by TNF‐α and also mediates TNF‐α stimulation of human lung fibroblasts. Further studies on the role of DCIP in airway inflammation and remodeling are warranted.