Regulation of Hypoxia‐Inducible Factors During Inflammation

Frede, Stilla; Berchner‐Pfannschmidt, Utta; Fandrey, Joachim

doi:10.1016/s0076-6879(07)35021-0

Cited by 94 publications

(120 citation statements)

References 73 publications

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“…Especially under conditions of inflammation, increased HIF-1␣ accumulation followed by activation of HIF-1 target genes under nonhypoxic conditions have been described (25,26). Depending on the cell type and the stimulus, the increase in HIF-1␣ seemed to occur on transcriptional, translational, or posttranslational cellular levels (27). HIF-1␣ accumulation after TNF-␣ and IL-1␤ stimulation was found to result from increased translation of the HIF-1␣ mRNA starting at an internal ribosomal entry site located within the nontranslated region of the first exon of the HIF-1␣ gene (28,29).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Inducible Factor (HIF) 1α Accumulation and HIF Target Gene Expression Are Impaired after Induction of Endotoxin Tolerance

Frede

Stockmann²,

Winning³

et al. 2009

The Journal of Immunology

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The oxygen-sensitive transcription factor hypoxia-inducible factor 1 (HIF-1) is known as the key regulator of hypoxia-induced gene expression. In addition to hypoxia, endotoxins such as bacterial LPS as well as proinflammatory cytokines have been shown to induce HIF-1, suggesting an integrative role for HIF-1 in conditions of hypoxia and inflammation. Cells can become tolerant to endotoxins by repetitive exposure to LPS. Herein, we studied the effect of endotoxin tolerance on HIF-1α accumulation and expression of HIF target genes in human monocytic cells and primary mouse peritoneal macrophages. Tolerant cells had reduced levels of HIF-1α under hypoxia, which was due to lowered levels of HIF-1α mRNA. HIF-1α expression is under control of NF-κB and increased DNA binding of the p52 subunit of NF-κB was found in tolerant cells. Knock down of p52 abolished the effects of endotoxin tolerance on HIF-1α expression, which suggest a negative regulatory role of p52 on HIF-1α transcription during endotoxin tolerance. Endotoxin tolerant cells showed diminished expression of the HIF target genes phosphoglycerate kinase 1 and adrenomedullin and reduced viability under hypoxic conditions, as well as a significantly reduced invasion. Peritoneal macrophages from endotoxin-tolerant mice made showed significantly reduced HIF-1α protein accumulation and subsequent HIF target gene expression. We conclude that endotoxin tolerance impairs HIF-1α induction which reduces the ability of monocytic cells to survive and function under hypoxic conditions.

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Section: Discussionmentioning

confidence: 99%

Hypoxia-Inducible Factor (HIF) 1α Accumulation and HIF Target Gene Expression Are Impaired after Induction of Endotoxin Tolerance

Frede

Stockmann²,

Winning³

et al. 2009

The Journal of Immunology

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“…Interestingly, this is caused by hypoxia, as well as by different mediators of inflammation (3). The most relevant transcription factors that are responsible for adaptation of cells to hypoxic and inflammatory conditions are hypoxia-inducible factors (HIFs), especially HIF-1 [the role of HIF-2 in inflammation still has to be clarified (4)], and NF-kB (1,(3)(4)(5)(6)(7)(8)(9). HIF-1 is a dimeric complex formed by two subunits: HIF-1a and HIF-1b (also known as aryl hydrocarbon nuclear translocator).…”

mentioning

confidence: 99%

Acute Hypoxia Induces HIF-Independent Monocyte Adhesion to Endothelial Cells through Increased Intercellular Adhesion Molecule-1 Expression: The Role of Hypoxic Inhibition of Prolyl Hydroxylase Activity for the Induction of NF-κB

Winning

Splettstoesser

Fandrey

et al. 2010

The Journal of Immunology

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“…On the other hand, the question of whether hypoxia exists in all of the cancer cells expressing the DP pattern must be considered. Currently, other studies have demonstrated hypoxia independent induction of HIF-1· (37)(38)(39)(40)(41). Transforming growth factor-ß1 (TGF-ß1) induces HIF-1 stabilization through the selective inhibition of HIF-1· associated prolyl hydroxylase 2 (PHD2) expression under normoxic conditions (38).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-inducible factor-1α expression predicts the response to 5-fluorouracil-based adjuvant chemotherapy in advanced gastric cancer

Miyazaki¹

2009

Oncol Rep

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Abstract. Hypoxia frequently occurs in various solid tumors, thereby accelerating cancer progression and treatment resistance. Hypoxia-inducible factor-1· (HIF-1·) plays a central role in tumor hypoxia by up-regulating the gene expression related to angiogenesis, cancer invasion and anti-apoptosis. The present study immunohistochemically investigated HIF-1· expression in 63 gastric cancer specimens. Those specimens were obtained from 44 patients that received 5-FU chemotherapy post-operatively whereas the remaining 19 patients did not. The immunostaining pattern of HIF-1· was classified into 3 patterns: diffuse-positive within the tumor (DP), positive at the invasive front of the tumor (FP) and negative (N). Thirty-six of 63 (57.1%) patients exhibited DP, 24 (38.1%) revealed FP and the remaining 3 (4.8%) patients were judged as N. The HIF-1· expression pattern grouped into DP and FP/N correlated with the clinicopathological factors and survival. As a result, the HIF-1· expression did not show a significant correlation with the clinicopathological factors, such as the depth of invasion, lymph node metastasis and tumor stage, nor patient survival in the 63 patients. However, in the 44 patients that underwent chemotherapy, patients with the FP/N pattern showed longer survival than those with the DP pattern. On the other hand, no significant difference in survival was found between the 2 patterns among 19 patients without the chemotherapy. These results indicated that the diffuse expression of HIF-1· in gastric tumors might lead to drug resistance against adjuvant chemotherapy using 5-FU. In conclusion, the assessment of the HIF-1· expression in the resected tissues might predict the drug response to adjuvant 5-FU chemotherapy in advanced gastric cancer patients.

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Regulation of Hypoxia‐Inducible Factors During Inflammation

Cited by 94 publications

References 73 publications

Hypoxia-Inducible Factor (HIF) 1α Accumulation and HIF Target Gene Expression Are Impaired after Induction of Endotoxin Tolerance

Hypoxia-Inducible Factor (HIF) 1α Accumulation and HIF Target Gene Expression Are Impaired after Induction of Endotoxin Tolerance

Acute Hypoxia Induces HIF-Independent Monocyte Adhesion to Endothelial Cells through Increased Intercellular Adhesion Molecule-1 Expression: The Role of Hypoxic Inhibition of Prolyl Hydroxylase Activity for the Induction of NF-κB

Hypoxia-inducible factor-1α expression predicts the response to 5-fluorouracil-based adjuvant chemotherapy in advanced gastric cancer

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