Proliferative activity of extracellular HIV-1 Tat protein in human epithelial cells: expression profile of pathogenetically relevant genes

Bettaccini, A; Baj, Andreina; Accolla, Roberto S.; Basolo, Fulvio; Toniolo, Antonio

doi:10.1186/1471-2180-5-20

Cited by 32 publications

(12 citation statements)

References 51 publications

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“…The observation that Tat increases LIM1215 proliferation is concordant with another report that showed the effects of Tat on the proliferative properties of epithelial cells [5]. Our data further suggests that LIM1215 + Tat cells are also able to expand significantly faster than LIM1215 parental cells in the absence of growth serum (Fig.…”

Section: Resultssupporting

confidence: 93%

“…In humans, Tat is required for maximum HIV pathogenicity [19] and is responsible for adverse biological effects in many different organs [34]. At the molecular level, Tat is reported to affect the expression of a wide range of genes in eukaryotic cells, including those involved in signalling, translation, proliferation, apoptosis and differentiation [5,9,31]. In addition, Tat is also a known oncogene in a number of transgenic experiments [3,16,24,30,33].…”

Section: Introductionmentioning

confidence: 98%

“…Furthermore, colonic epithelial cells have surface receptor proteins, namely galactosylceramide (GalCer) [12], CCR5 [28] and CXCR4 [20] that can be recognised and targeted by the HIV surface envelope glycoprotein, gp120. This capacity of HIV to target and infect epithelial cells may provide additional virus replication sites [1,5,10,13]. The fact that HIV is found in the GI tract, coupled with the observation that GI epithelial cells express receptors prompted us to consider how HIV may augment CRC.…”

Section: Introductionmentioning

confidence: 99%

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Oncogenic Properties of HIV-Tat in Colorectal Cancer Cells

Huynh¹,

Vincan²,

Mantamadiotis³

et al. 2007

CHR

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With the advent of Highly-Active-Anti-Retroviral-Therapy (HAART), HIV patients can expect to live beyond 10-15 years following diagnosis. An unexpected result of increased survival is the emergence of opportunistic, oncogenic virus-associated cancers such as Burkitt's lymphoma (Epstein-Barr Virus), cervical cancer (Human Papilloma Virus) and Kaposi's sarcoma (Kaposi's sarcoma-associated herpesvirus) in this immuno-compromised population. Furthermore, there are reports of colorectal cancers (CRC) in long-term HIV-AIDS survivors. Compared to the general, non-immuno-compromised population, long-term AIDS patients have 4 and 3.3-fold increased risk of developing colorectal and anorectal cancer respectively. Unlike oncogenic virus-associated cancers, CRC is not known to have a viral etiology. Our study aimed to investigate one aspect of HIV infection and colorectal carcinogenesis. We proposed that the HIV transactivator protein Tat; a protein with known oncogenic properties that is secreted and can re-enter non-infected cells may have a role in CRC. Using two CRC cell lines, LIM1215 and LIM2537 we found that Tat inhibits epithelial cyto-differentiation, blocks apoptosis in vitro and accelerates tumour formation in vivo. In addition, Tat significantly increases in vitro migration in the absence of foetal calf serum. These properties underpin CRC, and as HIV infection is initiated in the gut lymphoid system, these data provide a basis for the increased incidence of CRC in long term AIDS patients.

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Section: Resultssupporting

confidence: 93%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Oncogenic Properties of HIV-Tat in Colorectal Cancer Cells

Huynh¹,

Vincan²,

Mantamadiotis³

et al. 2007

CHR

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“…Similar elevations in plasma TGFβ level have been previously noted in HIV-infected patients compared with healthy controls, and associated with the progression of disease. 37 HIV-1 gp120 or Tat are sufficient to stimulate the production of TGFβ from hematopoietic stem cells or mammary epithelial cells in culture, respectively 21,38 . cART serves to suppress lentiviral replication and has been previously reported to decrease the level of TGFβ transcription in the lymph nodes of SIV-infected macaques 39 .…”

Section: Discussionmentioning

confidence: 99%

TGFβ-Mediated Downregulation of Thrombopoietin Is Associated With Platelet Decline in Asymptomatic SIV Infection

Pate

Lyons

Dorsey

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Thrombocytopenia is a known consequence of HIV infection, and decreased production of platelets has been previously implicated in the pathogenesis of platelet decline during asymptomatic infection. Thrombopoietin (THPO) drives platelet production by stimulating the maturation of bone marrow megakaryocytes, and can be transcriptionally down-regulated by cytokines that are increased during infection such as TGFβ and pf4. Design To determine whether transcriptional down-regulation of THPO contributed to decreased platelet production during asymptomatic infection in the SIV/ macaque model of HIV, we compared hepatic THPO mRNA levels to platelet number and megakaryocyte density. To identify potential inhibitory factors that decrease THPO transcription during asymptomatic infection, we measured TGFβ and pf4 plasma levels. To determine whether cART could correct platelet decline by altering cytokine levels, we measured TGFβ and pf4 in cART-treated SIV-infected macaques and compared these values to untreated SIV-infected macaques. Results Hepatic THPO transcription was down-regulated during asymptomatic SIV infection concurrent with platelet decline. Hepatic THPO mRNA levels correlated with bone marrow megakaryocyte density. In contrast, plasma TGFβ levels were inversely correlated with hepatic THPO transcription and bone marrow megakaryocyte density. With cART treatment, plasma TGFβ levels and platelet count returned to values similar to those in uninfected macaques. Conclusions TGFβ mediated downregulation of hepatic THPO may lead to decline in platelet number during asymptomatic SIV infection, and cART may prevent platelet decline by normalizing plasma TGFβ levels.

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“…IL-20 expression is detected uniformly throughout the epidermis in both disease types. Epithelial cell lines have also been shown to upregulate expression of IL-19 and IL-20 in response to HIV tat protein [25].…”

Section: Cellular Sources Of Il-20mentioning

confidence: 98%

Interleukin 20

Rich¹,

Kupper

2006

AIAAMC

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IL-20 is a member of the IL-10 family of cytokines that also includes IL-10, , and IL-26 as well as a number of viral homologs. Keratinocytes and monocytes in states of activation can produce IL-20. It transmits signals via two different cell-surface receptor complexes resulting in the activation of STAT3 in keratinocytes and other epithelial cells. Thus it appears to be primarily an inducible autocrine and paracrine factor that regulates proliferation and differentiation of keratinocytes in the context of inflammation. Several findings indicate that IL-20 mediates the hyperproliferation of keratinocytes associated with cutaneous inflammation. As such it is likely to have a central role in inflammatory skin diseases such as psoriasis and eczema. IL-20 also promotes the expansion of multipotential hematopoietic progenitor cells indicating a role beyond the response of epithelial cells to inflammation. Increased understanding of the biology of IL-20 may provide novel opportunities for diagnostic methods and therapeutic intervention.

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Proliferative activity of extracellular HIV-1 Tat protein in human epithelial cells: expression profile of pathogenetically relevant genes

Cited by 32 publications

References 51 publications

Oncogenic Properties of HIV-Tat in Colorectal Cancer Cells

Oncogenic Properties of HIV-Tat in Colorectal Cancer Cells

TGFβ-Mediated Downregulation of Thrombopoietin Is Associated With Platelet Decline in Asymptomatic SIV Infection

Interleukin 20

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