Interferon γ Repression of Collagen (COL1A2) Transcription Is Mediated by the RFX5 Complex

Xu, Yong; Wang, Lin; Butticè, Giovanna; Sengupta, Pritam K.; Smith, Barbara D.

doi:10.1074/jbc.m309003200

Cited by 37 publications

(62 citation statements)

References 55 publications

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“…Previously, we demonstrated that IFN-␥ stimulates the expression of RFX5 complex proteins and promotes the assembly of RFX5 complex on the collagen start site suggesting that RFX5 proteins are potential mediators for collagen repression by IFN-␥ (34,37). In the present investigation, we report that IFN-␥ promotes the recruitment of CIITA to the collagen promoter in part through binding to RFX5 complex.…”

supporting

confidence: 53%

“…FLAG-CIITA-(253-1130), FLAG-CIITA-(1-410), FLAG-CIITA-(253-410), and FLAG-CIITA-(⌬253-410) constructs were kindly provided by Dr. Matija Peterlin (21). Full-length His-RFXAP was constructed in this laboratory as previously described (37).…”

Section: Methodsmentioning

confidence: 99%

“…Dried DNA was dissolved in 50 l of deionized distilled water, and 10 l was used for each real-time PCR reaction. The primers for real-time PCR have been described previously (37).…”

Section: Methodsmentioning

confidence: 99%

“…Nuclear protein extracts were obtained as previously described (37). 100 -200 g of nuclear protein was used per DNA affinity pull-down assay.…”

Section: Methodsmentioning

confidence: 99%

“…Fibroblast Cells-Previously, we demonstrated that the expression of RFX5 complex proteins can be stimulated by IFN-␥ treatment in human lung fibroblasts (37). In this study, we examine the expression of CIITA in response to IFN-␥ stimulation in human lung fibroblasts with time.…”

Section: Ifn-␥ Up-regulates Ciita Expression In Human Lungmentioning

confidence: 99%

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Major Histocompatibility Class II Transactivator (CIITA) Mediates Repression of Collagen (COL1A2) Transcription by Interferon γ (IFN-γ)

Wang

Butticè

et al. 2004

Journal of Biological Chemistry

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supporting

confidence: 53%

Section: Methodsmentioning

confidence: 99%

“…Dried DNA was dissolved in 50 l of deionized distilled water, and 10 l was used for each real-time PCR reaction. The primers for real-time PCR have been described previously (37).…”

Section: Methodsmentioning

confidence: 99%

“…Nuclear protein extracts were obtained as previously described (37). 100 -200 g of nuclear protein was used per DNA affinity pull-down assay.…”

Section: Methodsmentioning

confidence: 99%

Section: Ifn-␥ Up-regulates Ciita Expression In Human Lungmentioning

confidence: 99%

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Major Histocompatibility Class II Transactivator (CIITA) Mediates Repression of Collagen (COL1A2) Transcription by Interferon γ (IFN-γ)

Wang

Butticè

et al. 2004

Journal of Biological Chemistry

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Adenosine signaling inhibits CIITA‐mediated MHC class II transactivation in lung fibroblast cells

Fang

Xia

et al. 2013

Eur J Immunol

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Keywords: Adenosine A2b signaling r CIITA r Epigenetics r MHC class II r Transcriptional regulation Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionAntigen-restricted activation of T lymphocytes, which are designed to eliminate intracellular pathogens, plays a critical role in adapCorrespondence: Dr. Yong Xu e-mail: yxu2005@gmail.com tive immunity [1]. By their expression of major histocompatibility complex (MHC) molecules, two groups of cells are specialized in presenting processed antigen to T cells: professional antigen presenting cells (p-APCs), which include B cells, dendritic cells, * These authors contributed equally to this work. . Efficient antigen presentation serves several critical pathobiological purposes. One of them is to combat the invasion of opportunistic microbes. Indeed, defective expression of MHC II molecules in fibroblast cells is associated with increased incidence of bacterial and viral infection [5]. Another example whereby the MHC II-dependent immune response plays a predominant role in host defense is the recognition and killing of cancer cells that express foreign epitopes. Mounting evidence has suggested that malignant cells employ a range of strategies to manipulate MHC II expression by fibroblast cells to facilitate evasion [6,7].Adenosine signaling is one of the biologically conserved pathways in mammals that regulates a range of life activities [8]. Recent investigations, however, reveal that adenosine signaling promotes carcinogenesis [9] and infectious diseases [10], indicating that it may target CIITA-mediated MHC II transactivation. Here, we report that adenosine signaling through the A2b receptor downregulates MHC II expression in lung fibroblast cells by repressing CIITA transcription via type III and IV promoters. Our data provide a novel rationale for the blockade of A2b adenosine signaling in the treatment of cancer and infectious disease. Results Adenosine signaling represses MHC II transcriptionWe have previously shown that MHC II expression is inducible by IFN-γ in lung fibroblast cells (IMR-90) in a CIITA-dependent manner [11]. To determine whether adenosine signaling could suppress MHC II expression, we treated IMR-90 cells with an adenosine receptor agonist adenosine-5 N-ethylcarboxamide (NECA). NECA downregulated the induction of HLA-DRα by IFN-γ at both mRNA (Fig. 1A) and protein (Fig. 1B) levels in a dose-response fashion. To examine whether the repression of MHC II expression by NECA took place at the transcription level, an HLA-DR-α promoter-reporter fusion construct was transfected into IMR-90 cells. As shown in Figure 1C, IFN-γ activated the promoter activity but NECA dampened the activation. Similar observations were made in primary mouse lung fibroblast cells (Supporting Information Fig. 1A and B). Therefore, activation of adenosine signaling in lung fibroblast cells is associated with attenuated MHC II transactivation by IFN-γ. Adenosine signaling represses CIITA expression via ...

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Scleroderma, fibroblasts, signaling, and excessive extracellular matrix

Ihn

2005

Curr Rheumatol Rep

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Excessive extracellular matrix (ECM) deposition in the skin, lung, and other organs is a hallmark of systemic sclerosis (SSc). The pathogenesis of SSc is still poorly understood, but increasing evidence suggests that various cytokines such as transforming growth factor (TGF)-beta and their signaling pathways are key mediators of tissue fibrosis as a consequence of ECM accumulation in the pathogenesis of fibrosis such as SSc. TGF-beta regulates diverse biologic activities including cell growth, cell death or apoptosis, cell differentiation, and ECM synthesis. TGF-beta is known to induce the expression of ECM proteins in mesenchymal cells, and to stimulate the production of protease inhibitors that prevent enzymatic breakdown of the ECM. This paper focuses on the possible role of ECM, various cytokines, especially TGF-beta signal transduction pathways in the pathogenesis of fibrosis in SSc.

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Interferon γ Repression of Collagen (COL1A2) Transcription Is Mediated by the RFX5 Complex

Cited by 37 publications

References 55 publications

Major Histocompatibility Class II Transactivator (CIITA) Mediates Repression of Collagen (COL1A2) Transcription by Interferon γ (IFN-γ)

Major Histocompatibility Class II Transactivator (CIITA) Mediates Repression of Collagen (COL1A2) Transcription by Interferon γ (IFN-γ)

Adenosine signaling inhibits CIITA‐mediated MHC class II transactivation in lung fibroblast cells

Scleroderma, fibroblasts, signaling, and excessive extracellular matrix

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