Reactive Oxygen Intermediates Are Involved in IL-8 Production Induced by Hyperosmotic Stress in Human Bronchial Epithelial Cells

Loitsch, Stefan; Mallinckrodt, C. von; Kippenberger, Stefan; Steinhilber, Dieter; Wagner, Thomas; Bargon, Joachim

doi:10.1006/bbrc.2000.3504

Cited by 47 publications

(35 citation statements)

References 42 publications

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“…Additional experiments in which lung slices were exposed to spores or spore buffer in the presence or absence of the inhibitor solvent (DMSO) revealed that this was due to suppression of the maximal lung cytokine and chemokine response to spores by DMSO (data not shown). A similar cytokine-suppressing effect of DMSO has been observed in A549 pulmonary epithelial cells and human bronchial epithelial cells and has been attributed to the properties of DMSO as a scavenger of free radicals (21,22).…”

Section: Vol 75 2007 Human Lung Response To B Anthracis Spores 3733supporting

confidence: 67%

Human Lung Innate Immune Response toBacillus anthracisSpore Infection

Chakrabarty

Booth

et al. 2007

Infect Immun

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Bacillus anthracis, the causative agent of inhalational anthrax, enters a host through the pulmonary system before dissemination. We have previously shown that human alveolar macrophages participate in the initial innate immune response to B. anthracis spores through cell signal-mediated cytokine release. We proposed that the lung epithelia also participate in the innate immune response to this pathogen, and we have developed a human lung slice model to study this process. Exposure of our model to B. anthracis (Sterne) spores rapidly activated the mitogen-activated protein kinase signaling pathways ERK, p38, and JNK. In addition, an RNase protection assay showed induction of mRNA of several cytokines and chemokines. This finding was reflected at the translational level by protein peak increases of 3-, 25-, 9-, 34-, and 5-fold for interleukin-6 (IL-6), tumor necrosis factor alpha, IL-8, macrophage inflammatory protein 1␣/␤, and monocyte chemoattractant protein 1, respectively, as determined by an enzyme-linked immunosorbent assay. Inhibition of individual pathways by UO126, SP600125, and SB0203580 decreased induction of chemokines and cytokines by spores, but this depended on the pathways inhibited and the cytokines and chemokines induced. Combining all three inhibitors reduced induction of all cytokines and chemokines tested to background levels. An immunohistochemistry analysis of IL-6 and IL-8 revealed that alveolar epithelial cells and macrophages and a few interstitial cells are the source of the cytokines and chemokines. Taken together, these data showed the activation of the pulmonary epithelium in response to B. anthracis spore exposure. Thus, the lung epithelia actively participate in the innate immune response to B. anthracis infection through cell signal-mediated elaboration of cytokines and chemokines.

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Section: Vol 75 2007 Human Lung Response To B Anthracis Spores 3733supporting

confidence: 67%

Human Lung Innate Immune Response toBacillus anthracisSpore Infection

Chakrabarty

Booth

et al. 2007

Infect Immun

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“…The effect seems to be promoter-specific and not caused by hyperosmolality (Loitsch et al, 2000;Takeda et al, 2001), because no increase was observed in RSV promoter-mediated transcription, and the effect was not caused by metabolically inactive L-glucose.…”

Section: Discussionmentioning

confidence: 94%

High glucose alone, as well as in combination with proinflammatory cytokines, stimulates nuclear factor kappa-B-mediated transcription in hepatocytes in vitro

Iwasaki

Kambayashi

Asai

et al. 2007

Journal of Diabetes and its Complications

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Diabetes mellitus is frequently associated with coagulation disorders such as coronary heart disease or stroke. We aimed to clarify the molecular mechanism whereby hyperglycemia causes the procoagulant state. The HuH7 human hepatocyte cells were treated with high glucose alone, or in combination with proinflammatory cytokines, and the effects on the activity of the transcription factor NF-B, which mediates the expression of acute phase and coagulation-related genes, were examined. The results showed that increasing the medium glucose concentration from 3 to 24 mM significantly enhanced the NF-B-luciferase activity by 40% in the presence of insulin. The effect was promoter-specific, and was not mimicked by comparable hyperosmolality with L-glucose. Proinflammatory cytokines such as interleukin-1 and TNF-also stimulated NF-B-dependent transcription, and showed an additive effect with high glucose. Similar effects were obtained on acute phase or coagulation/fibrinolysis-related gene promoters such as fibrinogen or PAI-1, all of which are shown to have NF-B-mediated transcription. Finally, pretreatment of the cells with an antioxidant PDTC completely abolished the effect of high glucose, and markedly attenuated that of TNF-, suggesting the involvement of reactive oxygen species. These results suggest that 1) high glucose as well as proinflammatory cytokines have positive effects on NF-B-mediated transcription in an additive manner, and enhance coagulation-related gene expression, and 2) the effects are mediated, at least partly, by the generation of oxidative stress, and may be responsible for the high prevalence of thrombotic disorders in the metabolic syndrome with diabetes, hyperinsulinemia, obesity and/or inflammation.

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“…61 More recently, antioxidants were found to inhibit hypo osmotic-induction of p38 MAPK in bronchial epithelial cells. 62 In contrast, JNK activity was found to be activated by antioxidants in Jurkat T cells 63 and inhibited in HeLa cells by ROI following treatment with phenethyl isothiocyanate. 64 However, we can not dismiss the possibility that the pathogenic effects of anthrax are mediated by another, as yet unidentified, LF-substrate.…”

Section: The Role Of Meks In the Pathogenesis Of Anthraxmentioning

confidence: 95%