IFN-γ Pretreatment Augments Immune Complex-Induced Matrix Metalloproteinase-1 Expression in U937 Histiocytes

Anderson, Fran; Game, Bryan A.; Atchley, D H; Xu, Minfu; Lopes‐Virella, Maria F.; Huang, Yan

doi:10.1006/clim.2001.5161

Cited by 10 publications

(8 citation statements)

References 35 publications

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“…T lymphocytes promote macrophage activation through the action of IFNγ that binds to IFNγ receptors and triggers the activation of JAK-STAT pathway. Studies have shown that priming of macrophages with IFNγ markedly enhances cellular responsiveness to inflammatory stimuli such as LPS (18), cytokines (21) and immune complexes (22). In the present study, we postulated that high glucose enhances the priming effect of IFNγ on macrophages.…”

Section: Discussionmentioning

confidence: 62%

High glucose and interferon gamma synergistically stimulate MMP-1 expression in U937 macrophages by increasing transcription factor STAT1 activity

Nareika

Sundararaj

et al. 2009

Atherosclerosis

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Recent Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions andComplications (DCCT/EDIC) and other clinical studies have reported that glucose control in patients with diabetes leads to a significant reduction of cardiovascular events and atherosclerosis, indicating that hyperglycemia plays an essential role in cardiovascular disease in diabetic patients. Although several mechanisms by which hyperglycemia promotes atherosclerosis have been proposed, it remains unclear how hyperglycemia promotes atherosclerosis by interaction with inflammatory cytokines. To test our hypothesis that hyperglycemia interplays with interferon gamma (IFNγ), a key factor involved in atherosclerosis, to up-regulate the expression of genes such as matrix metalloproteinases (MMPs) and cytokines that are involved in plaque destabilization, U937 macrophages cultured in medium containing either normal or high glucose were challenged with IFNγ and the expression of MMPs and cytokines were then quantified by real-time PCR and ELISA. Results showed that high glucose and IFNγ had a synergistic effect on the expression of MMP-1, MMP-9 and IL-1β. High glucose also enhanced IFNγ-induced priming effect on LPS-stimulated MMP-1 secretion. Furthermore, high glucose and IFNγ exert the synergistic effect on MMP-1 expression by enhancing STAT1 phosphorylation and STAT1 transcriptional activity. In summary, this study revealed a novel mechanism potentially involved in diabetes-promoted cardiovascular disease.

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Section: Discussionmentioning

confidence: 62%

High glucose and interferon gamma synergistically stimulate MMP-1 expression in U937 macrophages by increasing transcription factor STAT1 activity

Nareika

Sundararaj

et al. 2009

Atherosclerosis

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“…IFN-␥ can up-regulate MMPs and is increased in AAA, implicating it in AAA pathogenesis (4,21,23,24). To examine the role of IFN-␥ in AAA development, IFN-␥-deficient (IFN-␥ Ϫ/Ϫ ) mice underwent CaCl 2 aneurysm induction.…”

Section: Ifn-␥ Deficiency Prevents Aneurysm Formation and Mmp Up-regumentioning

confidence: 99%

Key Roles of CD4+ T Cells and IFN-γ in the Development of Abdominal Aortic Aneurysms in a Murine Model

Xiong

Zhao

Prall

et al. 2004

The Journal of Immunology

188

187

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Abdominal aortic aneurysm (AAA) is one of a number of diseases associated with a prominent inflammatory cell infiltrate and local destruction of structural matrix macromolecules. This inflammatory infiltrate is predominately composed of T lymphocytes and macrophages. Delineating specific contribution of these inflammatory cells and their cytokines in AAA formation is the key to understanding AAA and other chronic inflammatory disease processes. Our previous studies have demonstrated that macrophages are the major source of matrix metalloproteinase-9, which is required for aneurysmal degeneration in the murine AAA model. However, the role of CD4+ T cells, the most abundant infiltrates in aneurysmal aortic tissue, is uncertain. In the present study, we found that in the absence of CD4+ T cells, mice are resistant to aneurysm induction. Previous studies have shown that IFN-γ levels are increased in AAA. IFN-γ is a main product of T cells. Intraperitoneal IFN-γ was able to partially reconstitute aneurysms in CD4−/− mice. Furthermore, mice with a targeted deletion of IFN-γ have attenuation of MMP expression and inhibition of aneurysm development. Aneurysms in IFN-γ−/− mice can be reconstituted by reinfusion of competent splenocytes from the corresponding wild-type mice. This study demonstrates the pivotal role that T cells and the T cell cytokine, IFN-γ, play in orchestrating matrix remodeling in AAA. This study has important implications for other degenerative diseases associated with matrix destruction.

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“…Because it has been shown that Fc␥RIIa is the major receptor for CRP in leukocytes 25 and our recent studies have shown that both Fc␥RI and Fc␥RII are involved in the upregulation of MMP-1 expression in U937 histiocytes by immune complexes, 22,26 we examined the effect of CRP on MMP-1 secretion by U937 cells. Results showed that 100 g/mL of CRP stimulated MMP-1 secretion by 3-to 5-fold ( Figure 1) and the stimulation was concentration-dependent ( Figure I, available online at http://atvb.ahajournals.org).…”

Section: Crp Stimulates Mmp-1 Secretion and Mrna Expressionmentioning

confidence: 99%

“…22,26 To determine if CRP-stimulated MMP-1 expression is also ERK-dependent, we examined the effect of CRP on the phosphorylation of ERK1/2 in U937 cells by Western blot analysis with the use of both anti-phosphorylated ERK and anti-total ERK antibodies. 22 Our data showed that CRP stimulated phosphorylation of ERK, mainly ERK2, in a time-dependent manner with peak phosphorylation occurring at 5 minutes ( Figure 4).…”

Section: Crp Stimulates Erk Phosphorylationmentioning

confidence: 99%

C-Reactive Protein Stimulates MMP-1 Expression in U937 Histiocytes Through FcγRII and Extracellular Signal-Regulated Kinase Pathway:

Williams

Zhang

Game

et al. 2004

ATVB

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103

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Objective-It has been shown that plasma level of C-reactive protein (CRP) is an independent predictor for acute coronary syndromes and is associated with plaque weakening. However, the underlying mechanisms are not well understood. In this study, we investigated the effect of CRP on the expression of matrix metalloproteinase-1 (MMP-1) that has been implicated in plaque vulnerability by human U937 histiocytes and monocyte-derived macrophages. Methods and Results-Enzyme-linked immunosorbent assay of MMP-1 in conditioned medium showed that treatment of U937 cells with 100 g/mL of CRP for 24 hour led to a 3-to 5-fold increase in MMP-1 secretion. CRP also markedly stimulated MMP-1 release from human monocyte-derived macrophages. In contrast, CRP had no effect on tissue inhibitor of metalloproteinase-1 (TIMP-1) secretion. Northern blot showed that CRP upregulated MMP-1 mRNA expression. Collagenase activity assay showed that CRP increased collagen-degrading activity in cell-conditioned medium. Furthermore, results showed that the stimulation of MMP-1 secretion by CRP was inhibited by anti-CD32, but not by anti-CD64 antibody, and by mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) inhibitor PD98059. Finally, Western blot showed that CRP stimulated phosphorylation of extracellular signal-regulated kinase. Key Words: C-reactive protein Ⅲ matrix metalloproteinase Ⅲ arteriosclerosis Ⅲ gene expression C -reactive protein (CRP) is one of acute phase proteins that react to inflammation rapidly. 1 CRP is mainly produced by hepatocytes and its expression is upregulated by inflammatory cytokines such as interleukin-6. 1 Previous studies have well documented that CRP plays a role in host defense against bacterial pathogens and clearance of apoptotic and necrotic cells. 2 However, recent studies have provided evidence that CRP also has undesirable effects, such as promotion of inflammatory process and inflammationassociated atherosclerosis. For example, several investigations have shown that CRP induces the expression of adhesion molecules and chemokines in human endothelial cells [3][4][5] and stimulates release of tissue factor from monocytes. 6 The pathological studies also revealed that CRP is present in atherosclerotic lesions but not in the normal vessel wall. 5,[7][8][9] Furthermore, more than two dozen clinical studies published in the past decade have demonstrated a correlation between plasma CRP levels and acute coronary syndromes. 10 -13 All these studies suggest that CRP may be involved in the progression of atherosclerosis. Conclusions-ThisPlaque rupture and erosion are believed to be the key events that trigger the formation of thrombus and subsequent acute coronary syndromes. 14,15 Because a large number of studies have shown the correlation between plasma CRP levels and acute coronary syndromes, 10 -13 the possible role of CRP in plaque vulnerability has been investigated. A recent histopathological study showed that serum CRP level in patients who died of severe coronary artery disease w...

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IFN-γ Pretreatment Augments Immune Complex-Induced Matrix Metalloproteinase-1 Expression in U937 Histiocytes

Cited by 10 publications

References 35 publications

High glucose and interferon gamma synergistically stimulate MMP-1 expression in U937 macrophages by increasing transcription factor STAT1 activity

High glucose and interferon gamma synergistically stimulate MMP-1 expression in U937 macrophages by increasing transcription factor STAT1 activity

Key Roles of CD4+ T Cells and IFN-γ in the Development of Abdominal Aortic Aneurysms in a Murine Model

C-Reactive Protein Stimulates MMP-1 Expression in U937 Histiocytes Through FcγRII and Extracellular Signal-Regulated Kinase Pathway:

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