Gamma interferon: a central mediator in atherosclerosis

Leon, Martha Leticia Alfaro; Zuckerman, Steven H.

doi:10.1007/s00011-005-1377-2

Cited by 100 publications

(82 citation statements)

References 193 publications

(298 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…9 In this regard, CD4 1 CD28 null T cells secrete high amounts of IFN-c to activate macrophages, which produce metalloproteinases that degrade the extracellular matrix. 23,24 Furthermore, CD4 1 CD28 null T cells release perforin and granzymes that lyse endothelial cells and vascular smooth muscle cells. 25 In our study, we focused on CD8 1 CD57 1 T cells because cardiovascular mortality was independently associated only with the frequency of CD8 1 CD57 1 T cells and found that CD8 1 CD57 1 T cells also demonstrated senescent, pro-inflammatory and highly cytotoxic properties.…”

Section: Discussionmentioning

confidence: 99%

Characterization of CD8+CD57+ T cells in patients with acute myocardial infarction

Youn

Lee

et al. 2014

Cell Mol Immunol

View full text Add to dashboard Cite

Although T cells are known to be involved in the pathogenesis of coronary artery disease, it is unclear which subpopulation of T cells contributes to pathogenesis in acute myocardial infarction (MI). We studied the immunological characteristics and clinical impact of CD8 1 CD57 1 T cells in acute MI patients. The frequency of CD57 1 cells among CD8 1 T cells was examined in peripheral blood sampled the morning after acute MI events. Interestingly, the frequency of CD57 1 cells in the CD8 1 T-cell population correlated with cardiovascular mortality 6 months after acute MI. The immunological characteristics of CD8 1 CD57 1 T cells were elucidated by surface immunophenotyping, intracellular cytokine staining and flow cytometry. Immunophenotyping revealed that the CD8 1 CD57 1 T cells were activated, senescent T cells with pro-inflammatory and tissue homing properties. Because a high frequency of CD8 1 CD57 1 T cells is associated with short-term cardiovascular mortality in acute MI patients, this specific subset of CD8 1 T cells might contribute to acute coronary events via their pro-inflammatory and high cytotoxic capacities. Identification of a pathogenic CD8 1 T-cell subset expressing CD57 may offer opportunities for the evaluation and management of acute MI.

show abstract

Section: Discussionmentioning

confidence: 99%

Characterization of CD8+CD57+ T cells in patients with acute myocardial infarction

Youn

Lee

et al. 2014

Cell Mol Immunol

View full text Add to dashboard Cite

show abstract

“…Although an increased level of IFN-␥ is protective against acute viral infection, excessive production of IFN-␥ by NK cells can lead to increased pathology in the Shwartzman reaction to LPS, inflammatory bowel disease, and atherosclerosis (37)(38)(39)(40)(41)(42). Negative regulators such as ATF3 serve to modulate inflammation to a level appropriate for clearing a pathogen while preventing pathology caused by unrestrained inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

ATF3 regulates MCMV infection in mice by modulating IFN-γ expression in natural killer cells

Rosenberger

Clark

Treuting

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Activating transcription factor 3 (ATF3) is a negative regulator of proinflammatory cytokine expression in macrophages, and ATF3-deficient mice are more susceptible to endotoxic shock. Here, we demonstrate that ATF3 interacts with a cis-regulatory element of the IFN-␥ gene in natural killer (NK) cells, and that ATF3null NK cells show increased transcription and secretion of IFN-␥. NK cellderived IFN-␥ has previously been demonstrated to be protective against murine cytomegalovirus (MCMV) infection, and we show here that ATF3null mice exhibit decreased hepatic viral load and reduced liver histopathology upon challenge with MCMV. Reconstitution of NK-deficient mice with ATF3null NK cells more effectively controlled MCMV infection than mice reconstituted with WT cells, indicating that ATF3 acts within NK cells to regulate antiviral responses.cytomegalovirus ͉ infectious disease ͉ transcription factor ͉ viral immunity I nterferon (IFN)-␥ is a pleiotropic cytokine that functions at the innate-adaptive immune interface to promote antibacterial, antitumor, and antiviral responses (1). IFN-␥ is produced by natural killer (NK), NKT, CD4 ϩ , and/or CD8 ϩ T cells stimulated with the T helper (Th1)-skewing cytokines IL-12 and/or IL-18, with the cellular source of IFN-␥ depending on the specific disease model. Murine cytomegalovirus (MCMV) is a herpes virus that causes a systemic infection, and NK cell production of IFN-␥ early during infection is absolutely required for antiviral control (2). IFN-␥ has many effects during MCMV infection; in general, it modulates the host response by regulating the production of cytokines and chemokines to recruit and activate effector cells (3), increasing the levels of MHC class I (4), and activating antiviral effector mechanisms (5, 6). A similar role for IFN-␥ and NK cells in regulating herpes virus infection in humans has been suggested by genetic deficiency studies (ref. 7 and reviewed in refs. 8 and 9).Although much is known about the regulation of IFN-␥ expression in T cells, less is understood about this process in NK cells. It is known that the transcription factors and epigenetic modifications that regulate expression at the IFN-␥ locus are different in T cells and NK cells (10-12). The transcription factors SMAD3 (13), NF-Bp50 (14), Hlx (15), and Runx3 (16) negatively regulate IFN-␥ transcription in NK cells. Tight regulation of IFN-␥ expression is required to limit pathology; however, the impact of negative regulators of IFN-␥ expression in NK cells on disease has not been explored.Our laboratory previously identified activating transcription factor 3 (ATF3) as an important negative regulator of proinflammatory cytokine gene expression in macrophages by using transcriptional profiling and computational analysis (17). Here, we observe that ATF3 expression is highly induced in the livers of MCMV-infected mice and purified NK cells. Results ATF3null Mice Show Enhanced Protection Against MCMV Infection.The mouse liver is a major target organ for MCMV replication. We observed that ...

show abstract

“…Activated CD4 1 Tlymphocytes and macrophages are the predominant cell populations identifiable in atheromatous plaques (35,36). 6 /ml) were primed by incubation with interferon-g (100 ng/ml) for 24 h. After priming, the cells were incubated for 18 h with three different concentrations of OxLDL-ICs prepared with two different OxLDL antibodies with KLH-ICs at a concentration identical to the higher concentration of OxLDL-ICs.…”

Section: Discussionmentioning

confidence: 99%

“…1 T-cells do not fit neatly into the Th1-Th2 pattern, but they release predominantly interferon-g, a cytokine that is believed to play a key role in the development of atherosclerosis (36). This implies that cellmediated and humoral mechanisms may synergize in the atheromatous plaque to enhance the inflammatory reaction.…”

Section: Immune Complexes Containing Oxldl Are Proinflammatorymentioning

confidence: 99%

OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophages

Saad

Virella

Chassereau

et al. 2006

Journal of Lipid Research

109

100

View full text Add to dashboard Cite

show abstract

Gamma interferon: a central mediator in atherosclerosis

Cited by 100 publications

References 193 publications

Characterization of CD8+CD57+ T cells in patients with acute myocardial infarction

Characterization of CD8+CD57+ T cells in patients with acute myocardial infarction

ATF3 regulates MCMV infection in mice by modulating IFN-γ expression in natural killer cells

OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophages

Contact Info

Product

Resources

About