Upregulation of CD40 Expression on Endothelial Cells Infected with Human Cytomegalovirus

Maisch, Tim; Kropff, Barbara; Sinzger, Christian; Mach, Michael

doi:10.1128/jvi.76.24.12803-12812.2002

Cited by 21 publications

(20 citation statements)

References 51 publications

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“…However, in our experiments with primary endothelial cells, we used Fc-CD40L at similar concentrations as in our other experiments where the concentrations of Fc-CD40L were fully sufficient to induce strong responses and which were also sufficient to drive maturation of dendritic cells (data not shown). Of note, primary endothelial cells were often cotreated with other proinflammatory triggers (IL-4, INF-g, CMV infection) to increase CD40 expression and CD40 responses (53)(54)(55)(56). Conventional cultivated primary endothelial cells might thus not represent a suitable model to analyze the relevance of the CD40-Fn14 crosstalk in this type of cells in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…However, reports demonstrating robust effects of CD40 activation on endothelial cells are often based on in vivo studies. Indeed, studies analyzing endothelial CD40 functions in vitro typically report modest responses that only reach a very small percentage of the same response induced by TNF (53)(54)(55)(56). Furthermore, quite strong CD40L stimulation protocols have been used in these studies (10-20 mg/ml soluble CD40L or membrane CD40L transfectants) to see the comparable weak effects on CD40 activity (53)(54)(55)(56).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, studies analyzing endothelial CD40 functions in vitro typically report modest responses that only reach a very small percentage of the same response induced by TNF (53)(54)(55)(56). Furthermore, quite strong CD40L stimulation protocols have been used in these studies (10-20 mg/ml soluble CD40L or membrane CD40L transfectants) to see the comparable weak effects on CD40 activity (53)(54)(55)(56). However, in our experiments with primary endothelial cells, we used Fc-CD40L at similar concentrations as in our other experiments where the concentrations of Fc-CD40L were fully sufficient to induce strong responses and which were also sufficient to drive maturation of dendritic cells (data not shown).…”

Section: Discussionmentioning

confidence: 99%

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TWEAK Inhibits TRAF2-Mediated CD40 Signaling by Destabilization of CD40 Signaling Complexes

Salzmann

Lang

Rosenthal

et al. 2013

The Journal of Immunology

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We found recently that TNF-like weak inducer of apoptosis (TWEAK) and fibroblast growth factor–inducible-14 (Fn14) by virtue of their strong capability to reduce the freely available cytoplasmic pool of TNFR-associated factor (TRAF)2 and cellular inhibitors of apoptosis (cIAPs) antagonize the functions of these molecules in TNFR1 signaling, resulting in sensitization for apoptosis and inhibition of classical NF-κB signaling. In this study, we demonstrate that priming of cells with TWEAK also interferes with activation of the classical NF-κB pathway by CD40. Likewise, there was strong inhibition of CD40 ligand (CD40L)–induced activation of MAPKs in TWEAK-primed cells. FACS analysis and CD40L binding studies revealed unchanged CD40 expression and normal CD40L–CD40 interaction in TWEAK-primed cells. CD40L immunoprecipitates, however, showed severely reduced amounts of CD40 and CD40-associated proteins, indicating impaired formation or reduced stability of CD40L–CD40 signaling complexes. The previously described inhibitory effect of TWEAK on TNFR1 signaling has been traced back to reduced activity of the TNFR1-associated TRAF2–cIAP1/2 ubiquitinase complex and did not affect the stability of the immunoprecipitable TNFR1 receptor complex. Thus, the inhibitory effect of TWEAK on CD40 signaling must be based at least partly on other mechanisms. In line with this, signaling by the CD40-related TRAF2-interacting receptor TNFR2 was also attenuated but still immunoprecipitable in TWEAK-primed cells. Collectively, we show that Fn14 activation by soluble TWEAK impairs CD40L–CD40 signaling complex formation and inhibits CD40 signaling and thus identify the Fn14-TWEAK system as a potential novel regulator of CD40-related cellular functions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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TWEAK Inhibits TRAF2-Mediated CD40 Signaling by Destabilization of CD40 Signaling Complexes

Salzmann

Lang

Rosenthal

et al. 2013

The Journal of Immunology

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“…Moreover, HCMV infection induces CD40 on the surface of the infected cells that interact with CD40L and results in VEGF production [129]. Moreover, increased expression of integrin αvβ3, CXCR4/SDF-1, and CD44 may promote angiogenesis and initiate metastasis formation [130][131][132].…”

Section: Promotion Of Tumorigenesis By Human Cytomegalovirus (Hcmv) Imentioning

confidence: 99%

Promotion of Tumorigenesis and Clinical Implications of Viral Infection in Breast Cancer

Rahbar¹

2015

J Carcinog Mutagen

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The prevalence of breast cancer is rising worldwide. The main cause of death from breast cancer is distant metastasis, which occurs within 3 years after diagnosis in 10-15% of patients. The initiation and progression of breast cancer have been related to both external and internal factors, including viral infection. Human cytomegalovirus infection (HCMV) is common in breast cancer and metastases, and high tumor levels of HCMV appear to worsen outcomes. HCMV can increase the malignant behavior of tumor cells by modulating multiple cellular regulatory and signaling pathways and enhance the proliferation, survival, invasion, motility, and adhesion of tumor cells. Although HCMV seems to have an oncomodulatory role in breast cancer, definitive evidence for a causal role is lacking, and further studies are needed. The current review will discuss evidence that links viral infections to breast cancer.

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“…Adherent thrombi are easily formed at lesions where ECs are damaged in vivo. CD40 can be expressed at high levels on the surfaces of CMV-infected ECs, and an increased level of E-selectin can be induced on those cells after stimulation with CD40 ligand (11). CMV increases the levels of inflammatory cytokines, such as interleukin-1␤, interleukin-6, or tumor necrosis factor alpha, and growth factors, such as platelet-derived growth factor or transforming growth factor ␤ (1, 7, 14).…”

mentioning

confidence: 99%

Acute Cytomegalovirus Infection and Transient Carotid Intimal-Medial Thickening in a Young, Otherwise Healthy Woman

et al. 2003

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Upregulation of CD40 Expression on Endothelial Cells Infected with Human Cytomegalovirus

Cited by 21 publications

References 51 publications

TWEAK Inhibits TRAF2-Mediated CD40 Signaling by Destabilization of CD40 Signaling Complexes

TWEAK Inhibits TRAF2-Mediated CD40 Signaling by Destabilization of CD40 Signaling Complexes

Promotion of Tumorigenesis and Clinical Implications of Viral Infection in Breast Cancer

Acute Cytomegalovirus Infection and Transient Carotid Intimal-Medial Thickening in a Young, Otherwise Healthy Woman

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