Dendritic cell-derived interferon-gamma-induced protein mediates tumor necrosis factor-alpha stimulation of human lung fibroblasts.
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)-alpha. Total proteins from lung fibroblasts were separated by 2-DE, and differentially expressed proteins were identified by MALDI-TOF MS. TNF-alpha 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 (alpha subunit) in human lung fibroblasts. In particular, dendritic cell-derived interferon-gamma-induced protein (DCIP) was upregulated by TNF-alpha in lung fibroblasts and its biological function is at present unknown. We found that TNF-alpha-induced DCIP expression was dependent on the transcription factor interferon regulatory factor-1. DCIP-selective antisense oligodeoxynucleotide inhibited the expression of TNF-alpha-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-alpha. We have demonstrated for the first time that DCIP is upregulated by TNF-alpha and also mediates TNF-alpha stimulation of human lung fibroblasts. Further studies on the role of DCIP in airway inflammation and remodeling are warranted.
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Wupeng
W
Liao
Zhang
Z
Bao
Chang
C
Cheng
Yu-Keung
YK
Mok
W S Fred
WS
Wong
D002478:Cells, Cultured; D003713:Dendritic Cells / Q000737:chemistry*; D015180:Electrophoresis, Gel, Two-Dimensional; D005347:Fibroblasts / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008168:Lung / Q000166:cytology*; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010449:Peptide Mapping; D020543:Proteome / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D000076106:SAM Domain and HD Domain-Containing Protein 1; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology*
C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D016376:Oligonucleotides, Antisense; D020543:Proteome; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins