Hypoxia-induced IL-6 production is associated with activation of MAP kinase, HIF-1, and NF-κB on HEI-OC1 cells

Jeong, Hyun‐Ja; Hong, Seung‐Heon; Park, Raekil; Shin, Taekyun; An, Nyeon‐Hyoung; Kim, Hyung-Min

doi:10.1016/j.heares.2005.04.003

Cited by 68 publications

(52 citation statements)

References 52 publications

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“…3A) did not reverse the effects of hypoxia on Ah-responsiveness. It has also been reported that in some cell types, that hypoxia induced p65 and NFκB (Jeong, Hong, Park, Shin, An, and Kim, 2005) and p65 can inhibit Ah-responsiveness and induction of CYP1A1 by TCDD (Ke, Rabson, Germino, Gallo, and Tian, 2001;Tian, Ke, Denison, Rabson, and Gallo, 1999). However, results in Figure 5A demonstrate that hypoxia does not affect p65 expression in ZR-75 cells; moreover, this protein is expressed primarily in the cytosol under all the treatment conditions.…”

Section: Discussionmentioning

confidence: 57%

“…Stress responsive NFκB signaling also inhibits AhR-mediated transactivation (Ke et al, 2001;Tian et al, 1999) and in some cells, hypoxic conditions increase p65 and NFκB expression (Jeong et al, 2005). Therefore, we investigated interactions between hypoxia, NFκB and Ah-responsiveness in ZR-75 cells treated with DMSO or TCDD for 6 and 24 hr under normoxia or hypoxia (Fig.…”

Section: Results Inmentioning

confidence: 99%

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Cobaltous chloride and hypoxia inhibit aryl hydrocarbon receptor-mediated responses in breast cancer cells

Khan

Liu

Stoner

et al. 2007

Toxicology and Applied Pharmacology

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The aryl hydrocarbon receptor (AhR) is expressed in estrogen receptor (ER)-positive ZR-75 breast cancer cells. Treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces CYP1A1 protein and mRNA levels and also activates inhibitory AhR-Erα crosstalk associated with hormone-induced reporter gene expression. In ZR-75 cells grown under hypoxia, induction of these AhR-mediated responses by TCDD was significantly inhibited. This was not accompanied by decreased nuclear AhR levels or decreased interaction of the AhR complex with the CYP1A1 gene promoter as determined in a chromatin immunoprecipitation assay. Hypoxia-induced loss of Ah-responsiveness was not associated with induction of hypoxia-inducible factor-1α or other factors that sequester the AhR nuclear translocation (Arnt) protein, and overexpression of Arnt under hypoxia did not restore Ah-responsiveness. The p65 subunit of NFκB which inhibits AhR-mediated transactivation was not induced by hypoxia and was primarily cytosolic in ZR-75 cells grown under hypoxic and normoxic conditions. In ZR-75 cells maintained under hypoxic conditions for 24 hr, BRCA1 (an enhancer of AhR-mediated transactivation in breast cancer cells) was significantly decreased and this contributed to loss of Ah-responsiveness. In cells grown under hypoxia for 6 hr, BRCA1 was not decreased, but induction of CYP1A1 by TCDD was significantly decreased. Cotreatment of ZR-75 cells with TCDD plus the protein synthesis inhibitor cycloheximide for 6 hr enhanced CYP1A1 expression in cells grown under hypoxia and normoxia. These results suggest that hypoxia rapidly induces protein(s) that inhibit Ah-responsiveness and these may be similar to constitutively expressed inhibitors of Ahresponsiveness (under normoxia) that are also inhibited by cycloheximide.

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Section: Discussionmentioning

confidence: 57%

Section: Results Inmentioning

confidence: 99%

Cobaltous chloride and hypoxia inhibit aryl hydrocarbon receptor-mediated responses in breast cancer cells

Khan

Liu

Stoner

et al. 2007

Toxicology and Applied Pharmacology

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“…1A, B, and E). HIF-1␣ has been shown to regulate inflammation and enhance expression of cytokines, including IL-6 (36,37). HIF-1␣ is rapidly targeted for degradation by prolyl hydroxylases (PHDs) but is stabilized through inactivation of PHDs by iron limitation, hypoxia, or the dioxygenase inhibitor DMOG (38).…”

Section: Enterobactin and Ent؉lcn2 Induce Distinct Gene Expression Anmentioning

confidence: 99%

Bacterial Siderophores That Evade or Overwhelm Lipocalin 2 Induce Hypoxia Inducible Factor 1α and Proinflammatory Cytokine Secretion in Cultured Respiratory Epithelial Cells

et al. 2014

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e Iron is essential for many cellular processes and is required by bacteria for replication. To acquire iron from the host, pathogenic Gram-negative bacteria secrete siderophores, including enterobactin (Ent). However, Ent is bound by the host protein lipocalin 2 (Lcn2), preventing bacterial reuptake of aferric or ferric Ent. Furthermore, the combination of Ent and Lcn2 (Ent؉Lcn2) leads to enhanced secretion of interleukin-8 (IL-8) compared to that induced by either stimulus alone. Modified or structurally distinct siderophores, including yersiniabactin (Ybt) and glycosylated Ent (GlyEnt, or salmochelin), deliver iron to bacteria despite the presence of Lcn2. We hypothesized that the robust immune response to Ent and Lcn2 requires iron chelation rather than the Ent؉Lcn2 complex itself and also can be stimulated by Lcn2-evasive siderophores. To test this hypothesis, cultured respiratory epithelial cells were stimulated with combinations of purified siderophores and Lcn2 and analyzed by gene expression microarrays, quantitative PCR, and cytokine immunoassays. Ent caused HIF-1␣ protein stabilization, induced the expression of genes regulated by hypoxia-inducible factor 1␣ (HIF-1␣), and repressed genes involved in cell cycle and DNA replication, whereas Lcn2 induced expression of proinflammatory cytokines. Iron chelation by excess Ent or Ybt significantly increased Lcn2-induced secretion of IL-8, IL-6, and CCL20. Stabilization of HIF-1␣ was sufficient to enhance Lcn2-induced IL-6 secretion. These data indicate that respiratory epithelial cells can respond to bacterial siderophores that evade or overwhelm Lcn2 binding by increasing proinflammatory cytokine production.

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“…The second is a sustained stable phase called long-term heat acclimation, during which a new homeostasis is achieved [19,20]. Hypoxia is a condition of decreased oxygen (O 2 ) levels that elicits homeostatic responses aimed at counteracting the negative effects of O 2 depletion [21]. Hypoxia induces the expression of several genes, such as erythropoietin [22], vascular endothelial growth factor [23], and other agents that favor the adaptation of the organism to the decreased availability of O 2 .…”

Section: Introductionmentioning

confidence: 99%

“…Hypoxia induces the expression of several genes, such as erythropoietin [22], vascular endothelial growth factor [23], and other agents that favor the adaptation of the organism to the decreased availability of O 2 . Hypoxia is an essential developmental and physiological stimulus that plays a key role in the pathophysiology of heart disease, cancer, neuron death, cerebrovascular disease and chronic lung disease, which are the most common cause of mortality in Western nations [21,23]. These findings prompted our interest in the acclimatization processes and possibly influence of these factors on reproductive function of the female rat.…”

Section: Introductionmentioning

confidence: 99%

Changes in ambient temperature and oxygenation during the proestrus do not affect duration, regularity and repeatability of the estrus cycle in female rats.

Baran

Jakiel²,

Wójcik³

2009

Folia Histochem Cytobiol.

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Abstract:There are a lot of factors affecting the release of hormones from the anterior part of pituitary gland and their interactions with other parts of the endocrine, nervous and immune systems. The special significance of the proestrus phase of the estrous cycle of the rat, during which LH and FSH levels increase, followed by ovulation is known. The short length of the estrous cycle and the well recognized sequence of vaginal lavage cytology make it useful for investigating the influence of a stressful environment on the reproductive function. Short duration and mild changes in environmental conditions is considered as a factor analogous to psychological stress. The study was undertaken to determine the effects of a short duration change in the ambient temperature and oxygenation (30 minutes) on the proestrus phase of reproductive cycle and on the repeatability and regularity of phases of the reproductive cycle of Wistar strain rats. The animals were kept under standard conditions and had food and water available ad libitum. The climatic chamber with automatically adjustable and monitored internal parameters (temperature, oxygenation, humidity) was used to develop stress conditions. An estimation of the vaginal lavage using the microscope was done to determine the estrous cycle. The animals were divided into 6 groups. On the day of experiment: the control group (CG) stayed in the climatic chamber for 30 minutes (ambient temperature 21°C, normoxia -21% O 2 ), the five test groups (TG -I -V) remained in the climatic chamber for 30 minutes, in the established environmental conditions (I -21°C, 10% O 2 ; II -10°C, 21% O 2 ; III -10°C, 10% O 2 ; IV -35°C, 21% O 2 ; V -35°C, 10% O 2 ). During the following days after the experiment, a microscopic estimation of vaginal lavage was collected over again. There were no changes of duration and sequence of the present estrous cycle and repeatability of the next cycles. Our results indicate that short duration change in the ambient conditions do not cause a disturbance in the hypothalamo -pituitary -gonadal axis, although it can activate adaptation mechanisms of the organism.

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Hypoxia-induced IL-6 production is associated with activation of MAP kinase, HIF-1, and NF-κB on HEI-OC1 cells

Cited by 68 publications

References 52 publications

Cobaltous chloride and hypoxia inhibit aryl hydrocarbon receptor-mediated responses in breast cancer cells

Cobaltous chloride and hypoxia inhibit aryl hydrocarbon receptor-mediated responses in breast cancer cells

Bacterial Siderophores That Evade or Overwhelm Lipocalin 2 Induce Hypoxia Inducible Factor 1α and Proinflammatory Cytokine Secretion in Cultured Respiratory Epithelial Cells

Changes in ambient temperature and oxygenation during the proestrus do not affect duration, regularity and repeatability of the estrus cycle in female rats.

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