Cytomegalovirus Infection Decreases Expression of Thrombospondin‐1 and ‐2 in Cultured Human Retinal Glial Cells: Effects of Antiviral Agents

Činátl, Jindřich; Bittoova, Martina; Margraf, Stefan; Vogel, Jens‐Uwe; Činátl, Jaroslav; Preiser, Wolfgang

doi:10.1086/315779

Cited by 28 publications

(13 citation statements)

References 44 publications

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“…Akt can phosphorylate and activate the inhibitor of NF-kB (IkB) kinase (IKK), which induces degradation of IkB and, therefore, increases NF-kB stability [92,94]. This mechanism is in concordance with the very rapid activation of NF-kB in a protein synthesis-independent manner, which was shown by different groups, including our own [95,96]. NF-kB has already been associated with suppression of apoptotic cascades [97].…”

Section: Hcmv Infection and Akt (Pkb) Signalingsupporting

confidence: 78%

Cytomegalovirus infection blocks apoptosis in cancer cells

Michaelis

Kotchetkov

Vogel

et al. 2004

CMLS, Cell. Mol. Life Sci.

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Recent pathological findings reveal a higher frequency of human cytomegalovirus (HCMV) in tumor cells from different tumors compared with surrounding tissues. Experimental investigations suggest possible supportive effects of HCMV for tumor development and progression. One HCMV effect on tumor cells is the inhibition of apoptosis, leading to the promotion of tumor cell survival. Decreased sensitivity to treatment-induced tumor cell death is a major reason for failure of anticancer chemotherapy. HCMV infection interferes with both the intrinsic and extrinsic cellular apoptosis pathways. HCMV promotes cell survival signaling influencing the tumor suppressor p53 and its relative p73, and stimulates the antiapoptotic Ras/Raf/MEK/Erk- and PI-3K-signaling pathways. Antiapoptotic effects mediated by HCMV are inhibited by antiviral treatment in cell culture. Therefore, a better understanding of the influence of HCMV infection on tumor cell apoptosis might translate into improved anti-cancer therapy.

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Section: Hcmv Infection and Akt (Pkb) Signalingsupporting

confidence: 78%

Cytomegalovirus infection blocks apoptosis in cancer cells

Michaelis

Kotchetkov

Vogel

et al. 2004

CMLS, Cell. Mol. Life Sci.

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“…TSP1 has been shown to be present in lower amounts in the supernatants of cultured KS cells compared with the supernatants of cultured endothelial cells, and also is sparsely expressed in KS lesions by immunohistochemical analysis (39). TSP1 and TSP2 have also both been reported to be decreased by HCMV infection in fibroblasts (13). Dysregulation of TSP1, angiopoietin 2, Cys-rich angiogenesis inducer (IGFBP10), and thrombomodulin by KSHV may all potentially contribute to angiogenesis in KS lesions, a prominent and defining feature of the disease.…”

Section: Discussionmentioning

confidence: 99%

Altered Patterns of Cellular Gene Expression in Dermal Microvascular Endothelial Cells Infected with Kaposi's Sarcoma-Associated Herpesvirus

Poole¹,

Yu²,

Kim³

et al. 2002

J Virol

105

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Kaposi's sarcoma (KS)-associated herpesvirus (KSHV; also called human herpesvirus 8) is believed to be the etiologic agent of Kaposi's sarcoma, multicentric Castleman's disease, and AIDS-associated primary effusion lymphoma. KSHV infection of human dermal microvascular endothelial cells (DMVEC) in culture results in the conversion of cobblestone-shaped cells to spindle-shaped cells, a characteristic morphological feature of cells in KS lesions. All spindle-shaped cells in KSHV-infected DMVEC cultures express the latency-associated nuclear protein LANA1, and a subfraction of these cells undergo spontaneous lytic cycle induction that can be enhanced by tetradecanoyl phorbol acetate (TPA) treatment. To study the cellular response to infection by KSHV, we used two different gene array screening systems to examine the expression profile of either 2,350 or 9,180 human genes in infected compared to uninfected DMVEC cultures in both the presence and absence of TPA. In both cases, between 1.4 and 2.5% of the genes tested were found to be significantly upregulated or downregulated. Further analysis by both standard and real-time reverse transcription-PCR procedures directly confirmed these results for 14 of the most highly upregulated and 13 of the most highly downregulated genes out of a total of 37 that were selected for testing. These included strong upregulation of interferon-responsive genes such as interferon response factor 7 (IRF7) and myxovirus resistance protein R1, plus upregulation of exodus 2 ␤-chemokine, RDC1 ␣-chemokine receptor, and transforming growth factor ␤3, together with strong downregulation of cell adhesion factors ␣ 4 -integrin and fibronectin plus downregulation of bone morphogenesis protein 4, matrix metalloproteinase 2, endothelial plasminogen activator inhibitor 1, connective tissue growth factor, and interleukin-8. Significant dysregulation of several other cytokine-related genes or receptors, as well as endothelial cell and macrophage markers, and various other genes associated with angiogenesis or transformation was also detected. Western immunoblot and immunohistochemical analyses confirmed that the cellular IRF7 protein levels were strongly upregulated during the early lytic cycle both in KSHV-infected DMVEC and in the body cavity-based lymphoma BCBL1 PEL cell line.

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“…31 The expression of TSP-1 can be observed in several ocular cell types and compartments, including the cornea, 32 conjunctiva, 33 iris and ciliary body, 34 retina, 35 choroidal vascular membrane, 36 retinal pigment epithelial cells, 36 and glial cells. 37 In addition, TSP-1 is detectable in the aqueous 38,39 and vitreous humor. 39 TSP-1 plays a significant role in ocular functions, including the maintenance of corneal avascularity.…”

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confidence: 99%

Thrombospondin-based antiangiogenic therapy

Zhang

Lawler

2007

Microvascular Research

127

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Ocular angiogenesis is one of the underlying causes of blindness and vision impairment and may occur in a spectrum of disorders, including diabetic retinopathy, neovascular age-related macular degeneration, retinal artery or vein occlusion, and retinopathy of prematurity. As such, strategies to inhibit angiogenesis by suppressing vascular endothelial growth factor activity have proven to be effective in the clinic for the treatment of eye diseases. A complementary approach would be to increase the level of naturally occurring inhibitors of angiogenesis, such as thrombospondin (TSP)-1. This article summarizes the development of TSP-1-based inhibitors of angiogenesis.

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Cytomegalovirus Infection Decreases Expression of Thrombospondin‐1 and ‐2 in Cultured Human Retinal Glial Cells: Effects of Antiviral Agents

Cited by 28 publications

References 44 publications

Cytomegalovirus infection blocks apoptosis in cancer cells

Cytomegalovirus infection blocks apoptosis in cancer cells

Altered Patterns of Cellular Gene Expression in Dermal Microvascular Endothelial Cells Infected with Kaposi's Sarcoma-Associated Herpesvirus

Thrombospondin-based antiangiogenic therapy

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