Differential gene expression modulated by the cytoplasmic domain of Fc gamma RIa (CD64) alpha-chain.
The cytoplasmic domain (CY) of the ligand-binding alpha-chain of the gamma-chain-associated FcRs can modulate receptor function such as phagocytosis, endocytosis, and intracellular trafficking of receptor-Ag complexes. To assess the potential role of the CY domain of human FcgammaRIa (CD64) alpha-chain in the transcriptional regulation of receptor-induced gene expression, we developed stably transfected murine macrophage cell lines expressing a full-length or a CY deletion mutant (tail-less) of human FcgammaRIa to analyze gene expression in response to receptor-specific cross-linking. Using the Affymetrix murine genome U74Av2 GeneChip array, we observed >100 candidate genes having > or =2-fold difference expression at 1.5 and 3 h after stimulation. Focusing on several immunologically related genes, we confirmed differential expression of M-CSF, macrophage inhibitory cytokine-1, leukocyte-specific protein 1, MIP-2, and IL-1R antagonist by RT-PCR and RNase protection assays. Analysis of mRNA stability indicated that the differential regulation of gene expression by the CY of the CD64 alpha-chain is at the level of gene transcription. Our results indicate that the CY of the CD64 alpha-chain modulates transcriptional activity induced by receptor-specific engagement in macrophages and provides a framework for understanding distinct expression profiles elicited by different Fc gamma-chain-associated receptors.
Qin
Hongwei
H
Department of Medicine, University of Alabama at Birmingham, 1900 University Boulevard, Birmingham, AL 35294-0006, USA.
Edberg
Jeffrey C
JC
Gibson
Andrew W
AW
Page
Grier P
GP
Teng
Lihong
L
Kimberly
Robert P
RP
D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000235:genetics / Q000276:immunology*; D020869:Gene Expression Profiling / Q000379:methods; D055436:Growth Differentiation Factor 15; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D007941:Leukemia P388; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins; D016328:NF-kappa B / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D014176:Protein Biosynthesis / Q000235:genetics / Q000276:immunology; D017434:Protein Structure, Tertiary / Q000235:genetics; D021122:Protein Subunits / Q000235:genetics / Q000502:physiology; D020871:RNA Stability / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D017452:Receptors, IgG / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012260:Ribonucleases / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology; D014162:Transfection
D002135:Calcium-Binding Proteins; D016207:Cytokines; C485701:Fcgr1 protein, mouse; C526140:GDF15 protein, human; C526141:Gdf15 protein, mouse; D055436:Growth Differentiation Factor 15; D015850:Interleukin-6; C057701:Lsp1 protein, mouse; D008840:Microfilament Proteins; D016328:NF-kappa B; D021122:Protein Subunits; D012333:RNA, Messenger; D017452:Receptors, IgG; D015534:Trans-Activators; D016173:Macrophage Colony-Stimulating Factor; D012260:Ribonucleases