HIF-1α protein is an essential factor for protection of myeloid cells against LPS-induced depletion of ATP and apoptosis that supports Toll-like receptor 4-mediated production of IL-6

Lall, Harjinder; Coughlan, Karen; Sumbayev, Vadim V.

doi:10.1016/j.molimm.2008.03.014

Cited by 33 publications

(47 citation statements)

References 18 publications

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“…When the level of ATP was restored by application of extracellular ATP, HIF-1a knockdown did not affect cell survival (as based on the results of the caspase 3 assay) or production of IL-6/TNFa. These data correspond to recent findings concerning the role of HIF1a protein in LPS-induced TLR4-mediated responses [11]. Therefore, one could possibly conclude that both membrane-associated (TLR4) and endosomal (TLR7/8) TLRs induce accumulation/activation of HIF-1a protein although different mechanisms are employed.…”

Section: Discussionsupporting

confidence: 91%

“…siRNA as well as the ssRNA fragment were transfected into THP-1 cells using DOTAP transfection reagent [11] according to the manufacturer's protocol.…”

Section: Transfer Of Ssrna Fragment and Hif-1a Sirna To Thp-1 Cellsmentioning

confidence: 99%

“…In general, HIF-1a as a transcription factor, plays a pivotal role in mediating angiogenesis, glycolysis and cell adhesion [10], which are critical for inflammation. However, it was found that HIF-1a protein is an essential factor for protection of myeloid cells against LPS-induced depletion of ATP and apoptosis [11], a fact that is crucial for TLR4-mediated production of pro-inflammatory cytokines. Based on these data, one could hypothesize that HIF-1a protein might also be involved in TLR7/8 downstream signaling.…”

Section: Introductionmentioning

confidence: 99%

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The involvement of hypoxia-inducible factor 1 alpha in Toll-like receptor 7/8-mediated inflammatory response

2009

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Section: Discussionsupporting

confidence: 91%

“…siRNA as well as the ssRNA fragment were transfected into THP-1 cells using DOTAP transfection reagent [11] according to the manufacturer's protocol.…”

Section: Transfer Of Ssrna Fragment and Hif-1a Sirna To Thp-1 Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The involvement of hypoxia-inducible factor 1 alpha in Toll-like receptor 7/8-mediated inflammatory response

2009

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“…TLR4 is closely involved in the development and progression of various inflammatory diseases, such as inflammatory bowel disease and atherosclerosis (9)(10)(11). A previous study has demonstrated that Hypoxia-inducible factor-1α mediates the toll-like receptor 4 signaling pathway leading to anti-tumor effects in human hepatocellular carcinoma cells under hypoxic conditions downstream signaling of TLR4 leads to an accumulation of HIF-1α, which is important for TLR4-dependent expression of proinflammatory cytokines (12). Certain studies have also demonstrated that bacteria or LPS-induced HIF-1α accumulation is TLR4 dependent in immune cells (12,13).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-inducible factor-1α mediates the toll-like receptor 4 signaling pathway leading to anti-tumor effects in human hepatocellular carcinoma cells under hypoxic conditions

Zhang

et al. 2016

Oncology Letters

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Abstract. Hypoxia-inducible factor-1α (HIF-1α) and toll-like receptor 4 (TLR4) are involved in numerous mechanisms of cancer biology, including cell proliferation and survival; however the interaction of the two factors under hypoxic conditions remains unclear. The present study investigated the in vitro mechanism that results in the suppression of tumor cell growth and cellular functions when HIF-1α is silenced. In the present study, the human hepatocellular carcinoma HepG2 cell line was transfected with short hairpin RNA (shRNA) against HIF-1α and cultured under hypoxic conditions (1% O 2 for 24 h). The expression of HIF-1α and various growth factors, including epidermal growth factor (EGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2), were examined using quantitative polymerase chain reaction and immunoblotting. Tumor growth was measured using a Cell Counting Kit-8 assay and tumor activity was measured using tumor cell invasion and migration assays. Lipopolysaccharide and TAK-242 were used to activate and inhibit TLR4, respectively, to observe the role of TLR4 in the HIF-1α silenced tumor cells. The expression of TLR4 signaling pathway associates, including myeloid differentiation primary response gene 88 (MyD88), apoptosis signal-regulating kinase 1 (ASK1), p38 mitogen-activated protein kinases and HIF-1α, were analyzed by western blot assay. Under hypoxic conditions, silencing of HIF-1α expression suppressed tumor cell growth and regulated the expression of tumor growth-associated genes, including EGF, HGF, VEGF and FG2. Suppression of tumor cell invasion and migration was also observed in the HIF-1α silenced HepG2 cell line. In addition, TLR4 was identified to be involved in HIF-1α and MyD88 accumulation, and activation of ASK1 and p38 were demonstrated to be critical for TLR4-mediated HIF-1α pathway. In conclusion, silencing of HIF-1α expression may induce anti-tumor effects under hypoxic conditions in HepG2 cells via the TLR4 mediated pathway, suggesting that the HIF-1α/TLR4 signaling cohort may act as a novel therapeutic target for the treatment of hepatocellular cancer.

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“…As a critical modulator for the expression of glycolytic enzymes, the absence of HIF-1α leads to a signiicant reduction of ATP availability in myeloid cells [52]. It was reported that a knockdown of HIF-1α protein led to a nulliied IL-6 production when exposed to LPS, suggesting that HIF-1α supported the LPS-dependent expression of IL-6 that, in turn, prevented the depletion of ATP and, therefore, protected myeloid cells against LPS/TLR4-induced apoptosis [53]. In human monocytes, LPS and hypoxia synergistically activated HIF-1 through p44/42 mitogen-activated protein kinases (MAPK) and NF-κB; however, repetitive exposure to LPS could induce tolerance to bacterial endotoxins and, hence, impair corresponding HIF-1α induction, which reduces the ability of monocytic cells to survive and function under low oxygen [54,55].…”

Section: Hypoxia and Periodontal Immunitymentioning

confidence: 99%

Role of the Hypoxia-Inducible Factor in Periodontal Inflammation

Wang¹,

Chen²,

Leung³

2017

Hypoxia and Human Diseases

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Human periodontitis is a chronic inlammatory disease induced by opportunistic Gramnegative anaerobic bacteria at the tooth-supporting apparatus. Within the gingivitisafected sulcus or periodontal pocket, the resident anaerobic bacteria interact with the host inlammatory reactions leading to a lower oxygen or hypoxic environment. A cellular/tissue oxygen-sensing mechanism and its appropriate regulation are needed to assist tissue adaptation to natural/pathology-induced variations in oxygen availability. In this chapter, we reviewed the biological relevance of hypoxia in periodontal/oral cellular development, epithelial barrier function, periodontal inlammation, and immunity. The role of hypoxia-inducible factor-1α in pathogen-host cross talk and alveolar bone homeostasis was also discussed. The naturally occurring pathophysiological process of hypoxia appeared to entail fundamental relevance for periodontal defense and regeneration.

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HIF-1α protein is an essential factor for protection of myeloid cells against LPS-induced depletion of ATP and apoptosis that supports Toll-like receptor 4-mediated production of IL-6

Cited by 33 publications

References 18 publications

The involvement of hypoxia-inducible factor 1 alpha in Toll-like receptor 7/8-mediated inflammatory response

The involvement of hypoxia-inducible factor 1 alpha in Toll-like receptor 7/8-mediated inflammatory response

Hypoxia-inducible factor-1α mediates the toll-like receptor 4 signaling pathway leading to anti-tumor effects in human hepatocellular carcinoma cells under hypoxic conditions

Role of the Hypoxia-Inducible Factor in Periodontal Inflammation

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