The role of HIF-1 in up-regulating MICA expression on human renal proximal tubular epithelial cells during hypoxia/reoxygenation

Luo, Lei; Lu, Jun; Liang, Wei; Long, Dan; Guo, Jia; Shan, Juan; Li, Fu S; Lu, Ping; Li, Ping Y; Li, Feng

doi:10.1186/1471-2121-11-91

Cited by 44 publications

(41 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is in accordance with data showing that HIF-1α is necessary for the hypoxia-induced reduction of the MICA membrane expression on malignantly transformed cells (Barsoum et al 2011;Yamada et al 2012). However, in nontransformed human cells, MICA/B membrane expression was found to be upregulated by a hypoxia/reoxygenationinduced HIF-1α overexpression (Luo et al 2010;Wei et al 2010).…”

Section: Discussionsupporting

confidence: 92%

A hypoxia-induced decrease of either MICA/B or Hsp70 on the membrane of tumor cells mediates immune escape from NK cells

Schilling

Tetzlaff

Konrad

et al. 2015

Cell Stress and Chaperones

View full text Add to dashboard Cite

Recent findings suggest that hypoxia of the tumor microenvironment contributes to immune escape from natural killer (NK) cell-mediated cytotoxicity. Heat shock protein 70 (Hsp70) and the stress-regulated major histocompatibility class I chain-related protein A and B (MICA/B) both serve as ligands for activated NK cells when expressed on the cell surface of tumor cells. Herein, we studied the effects of hypoxia and hypoxia-inducible factor-1α (HIF-1α) on the membrane expression of these NK cell ligands in H1339 with high and MDA-MB-231 tumor cells with low basal HIF-1α levels and its consequences on NK cell-mediated cytotoxicity. We could show that a hypoxia-induced decrease in the membrane expression of MICA/B and Hsp70 on H1339 and MDA-MB-231 cells, respectively, is associated with a reduced sensitivity to NK cell-mediated lysis. A knockdown of HIF-1α revealed that the decreased surface expression of MICA/B under hypoxia is dependent on HIF-1α in H1339 cells with high basal HIF-1α levels. Hypoxia and HIF-1α did not affect the MICA/B expression in MDA-MB-231 cells but reduced the Hsp70 membrane expression which in turn also impaired NK cell recognition. Furthermore, we could show that the hypoxia-induced decrease in membrane Hsp70 is independent of HIF-1α in MDA-MB-231. Our data indicate that hypoxia-induced downregulation of both NK cell ligands MICA/B and Hsp70 impairs NK cell-mediated cytotoxicity, whereby only MICA/B appears to be regulated by HIF-1α.

show abstract

Section: Discussionsupporting

confidence: 92%

A hypoxia-induced decrease of either MICA/B or Hsp70 on the membrane of tumor cells mediates immune escape from NK cells

Schilling

Tetzlaff

Konrad

et al. 2015

Cell Stress and Chaperones

View full text Add to dashboard Cite

show abstract

“…These results show that the effects of hypoxia on the expression of cell surface MICA are mediated by HIF-1α. It has been reported that HIF-1α upregulates the expression of MICA in human renal proximal tubular epithelial cells and cardiomyocytes (25,26). The effects of HIF-1α on the expression of cell surface MICA may be different between tumor cells and normal cells.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia downregulates the expression of cell surface MICA without increasing soluble MICA in osteosarcoma cells in a HIF-1α-dependent manner

Yamada

Yamanegi

Ohyama

et al. 2012

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. Tumor cells express NKG2D ligands on their cell surface, which are the ligands of the activating receptor, NKG2D, that is expressed on the surface of NK cells. The binding of NK cells to tumor cells through the interaction of NKG2D and its ligands induces the cytolysis of the tumor cells. In the present study, we investigated the effects of hypoxia on the expression of NKG2D ligands on the surface of human osteosarcoma cells using three cell lines. To produce hypoxic and normoxic conditions, the osteosarcoma cell lines were cultured under 1 and 20% O 2 conditions, respectively. The osteosarcoma cells expressed NKG2D ligands such as MHC class I-related chain molecules A and B (MICA and MICB) and the UL16-binding proteins 1, 2 and 3 (ULBP 1, 2 and 3). MICA was the most frequently expressed NKG2D ligand in the osteosarcoma cells. Hypoxia decreased the expression of cell surface MICA only without increasing the secretion of soluble MICA, which is produced by proteolytic cleavage of cell surface MICA. Hypoxia consistently decreased the susceptibility of the osteosarcoma cells to the cytotoxicity of the NK cells. Hypoxia induced the expression of hypoxia-inducible factor-1α (HIF-1α), and knockdown of the expression of HIF-1α using small interfering RNA increased the expression of cell surface MICA and concomitantly increased the level of soluble MICA. Hypoxia decreased the production of nitric oxide (NO) metabolites (nitrite and nitrate), thus, indicating a decreasing effect on NO production. However, a NO donor, NOC18, decreased the expression of cell surface MICA without any apparent effects on the expression of HIF-1α under both hypoxic and normoxic conditions. The present results indicate that hypoxia downregulates the expression of cell surface MICA without increasing the level of soluble MICA in a HIF-1α-dependent manner and suggest that the effects of hypoxia are not linked to the hypoxia-induced reduction of NO production.

show abstract

“…Ischaemia is also intimately associated with tissue hypoxia. Recent work has suggested a role for HIF in the regulation of inflammatory tissue damage that is associated with ischaemic disease in the brain and kidney 126–128 .…”

Section: Hypoxia In Pathological Immune Nichesmentioning

confidence: 99%

Regulation of immunity and inflammation by hypoxia in immunological niches

2017

View full text Add to dashboard Cite

Immunological niches are focal sites of immune activity that can have varying microenvironmental features. Hypoxia is a feature of physiological and pathological immunological niches. The impact of hypoxia on immunity and inflammation can vary depending on the microenvironment and immune processes occurring in a given niche. In physiological immunological niches, such as the bone marrow, lymphoid tissue, placenta and intestinal mucosa, physiological hypoxia controls innate and adaptive immunity by modulating immune cell proliferation, development and effector function, largely via transcriptional changes driven by hypoxia-inducible factor (HIF). By contrast, in pathological immunological niches, such as tumours and chronically inflamed, infected or ischaemic tissues, pathological hypoxia can drive tissue dysfunction and disease development through immune cell dysregulation. Here, we differentiate between the effects of physiological and pathological hypoxia on immune cells and the consequences for immunity and inflammation in different immunological niches. Furthermore, we discuss the possibility of targeting hypoxia-sensitive pathways in immune cells for the treatment of inflammatory disease.

show abstract

The role of HIF-1 in up-regulating MICA expression on human renal proximal tubular epithelial cells during hypoxia/reoxygenation

Cited by 44 publications

References 32 publications

A hypoxia-induced decrease of either MICA/B or Hsp70 on the membrane of tumor cells mediates immune escape from NK cells

A hypoxia-induced decrease of either MICA/B or Hsp70 on the membrane of tumor cells mediates immune escape from NK cells

Hypoxia downregulates the expression of cell surface MICA without increasing soluble MICA in osteosarcoma cells in a HIF-1α-dependent manner

Regulation of immunity and inflammation by hypoxia in immunological niches

Contact Info

Product

Resources

About