IL‐4 enhances hypoxia induced HIF‐1α protein levels in human transformed intestinal cells

Scharte, Marion; Jurk, Kerstin; Kehrel, Beate E.; Zarbock, Alexander; Aken, Hugo Van; Singbartl, Kai

doi:10.1016/j.febslet.2006.10.053

Cited by 17 publications

(17 citation statements)

References 39 publications

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“…This parallels the findings that HIF-1␣ is present at detectable levels under normoxia in some skeletal cells and during PMA-mediated differentiation in monocytic cell lines (THP1 and U937) [41][42][43]. In addition, cytokines, such as TNF-␣, interferon-␥, IL1␤ and IL4 increase HIF-1␣ mRNA and/or protein levels during normoxia [44]. Ascertaining whether HIF-1␣ expression in DC under normoxic conditions is associated with the presence of IL4 and GM-CSF in the culture medium during the induction of DC differentiation should be the object of further investigation.…”

Section: Discussionsupporting

confidence: 86%

Expression of hypoxia-inducible factor 1α in mononuclear phagocytes infected with Leishmania amazonensis

et al. 2007

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Section: Discussionsupporting

confidence: 86%

Expression of hypoxia-inducible factor 1α in mononuclear phagocytes infected with Leishmania amazonensis

et al. 2007

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“…Subsequent studies have demonstrated that inflammatory cytokines and inflammatory mediators such as IL-4 are critical regulators of the activation of HIF-1␣ (17,41). Interestingly, some of these inductions have been shown to be equal or greater than the hypoxic induction of HIF-1␣.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory stimulation and hypoxia cooperatively activate HIF-1α in bronchial epithelial cells: involvement of PI3K and NF-κB

Jiang

Zhu

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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The transcription factor hypoxia-inducible factor (HIF)-1 plays a central physiological role in oxygen and energy homeostasis, and is activated during hypoxia by stabilization of the subunit HIF-1α. Recent studies have demonstrated that non-hypoxic stimuli can also activate HIF-1α in a cell-specific manner. Here, we demonstrate that stimulation of BEAS-2B cells and primary human bronchial epithelial cells by proinflammatory cytokines TNFα/IL-4 strongly induced expression and transcriptional activity of HIF-1α under normoxic conditions and amplified hypoxic HIF-1α activation. TNFα/IL-4 stimulated de novo HIF-1α gene transcription and translation rather than affected HIF-1α protein degradation and mRNA decay process. The activation of HIF-1α by TNFα/IL-4 was countered by the phosphoinositol 3-kinase (PI3K) inhibitor LY-294002 and rapamycin, an antagonist of mammalian target of rapamycin (mTOR), but not by inhibition of the MAPK pathway. In line, TNFα/IL-4 also activated NF-κB, whereas blocking of NF-κB by an inhibitor or silencing NF-κB subunit p65 attenuated HIF-1α activation by TNFα/IL-4. We also found the collaborative induction of VEGF, a potent angiogenic factor required for airway remodeling, by TNFα/IL-4 and hypoxia partially via HIF-1α pathway in BEAS-2B cells. This study reports the previously unsuspected collaborative regulation of HIF-1α by TNFα/IL-4 and hypoxia in bronchial epithelial cells partially via PI3K-mTOR and NF-κB pathway, and thereby will lead to the elucidation of the importance of HIF-1 in integrating inflammatory and hypoxic response in the pathogenesis of airway diseases.

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“…Cytokines, such as interferon-alpha (IFN-), can increase the transcription of the HIF-1 subunit leading to an increase in HIF-1 protein [35]. In terms of protein stabilization, a series of reports suggest that HIF-1 protein can accumulate and trigger HIF-1-related signaling events through the activation of the PI3-kinase (PI3K) pathway [12,[36][37][38][39][40][41][42][43], production of nitric oxide (NO) [44][45][46][47][48] and up-regulation of cyclooxygenase-2 (COX-2) [49][50][51].…”

Section: Normoxic Induction Of Hif-1 Signaling During Inflammationmentioning

confidence: 99%

Targeting Hypoxia-Inducible Factor-1 (HIF-1) Signaling in Therapeutics: Implications for the Treatment of Inflammatory Bowel Disease

Hirota

Beck²,

MacDonald³

2009

IAD

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In response to hypoxia, adaptive hypoxia-inducible factor-1 (HIF-1) signaling events are activated to increase oxygen transport, anaerobic energy production and protective pathways to minimize ischemic tissue damage. Although the activation and subsequent induction of gene transcription by HIF-1 is normally associated with hypoxia, it is now established that HIF-1 signaling can be triggered under inflammatory conditions. HIF-1 has been implicated in a number of inflammatory diseases including rheumatoid arthritis, allergic asthma, psoriasis and inflammatory bowel disease (IBD). In the gastrointestinal tract, HIF-1-regulated gene products, such as vascular endothelial growth factor, intestinal trefoil factor and CD73, have been shown to provide protection in animal models of intestinal inflammation. Given the importance of HIF-1 signaling in the aforementioned diseases, there exists considerable interest in the development of methods to modulate HIF-1 expression as well as down-stream signaling events. This review examines HIF-1 signaling with a special focus on the gastrointestinal tract. The patents pertaining to the modulation of HIF-1 signaling are summarized, and their relevance to the treatment of inflammatory bowel disease is discussed.

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IL‐4 enhances hypoxia induced HIF‐1α protein levels in human transformed intestinal cells

Cited by 17 publications

References 39 publications

Expression of hypoxia-inducible factor 1α in mononuclear phagocytes infected with Leishmania amazonensis

Expression of hypoxia-inducible factor 1α in mononuclear phagocytes infected with Leishmania amazonensis

Inflammatory stimulation and hypoxia cooperatively activate HIF-1α in bronchial epithelial cells: involvement of PI3K and NF-κB

Targeting Hypoxia-Inducible Factor-1 (HIF-1) Signaling in Therapeutics: Implications for the Treatment of Inflammatory Bowel Disease

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