Basal expression of cyclooxygenase-2 and nuclear factor–interleukin 6 are dominant and coordinately regulated by interleukin 1 in the pancreatic islet

Sorli, Christopher H.; Zhang, Huijian; Armstrong, Michael B.; Rajotte, Ray V.; Maclouf, Jacques; Robertson, R. Paul

doi:10.1073/pnas.95.4.1788

Cited by 138 publications

(106 citation statements)

References 43 publications

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“…NF-B regulates the expressions of multiple proinflammatory genes that contribute to islet destruction, including Fas, iNOS, and cyclooxygenase-2 (Cetkovic-Cvrlje and Eizirik, 1994;Sorli et al, 1998;Darville and Eizirik, 2001). In addition, the promoters of other proinflammatory genes induced in -cells, including chemokines and adhesion molecules, also possess binding elements for NF-B (May and Ghosh, 1998).…”

Section: Discussionmentioning

confidence: 99%

Coptidis rhizoma extract protects against cytokine-induced death of pancreatic β-cells through suppression of NF-κ B activation

Kim

Kwon²,

Han³

et al. 2007

Exp Mol Med

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We demonstrated previously that Coptidis rhizoma extract (CRE) prevented S-nitroso-N-acetylpenicillamine-induced apoptotic cell death via the inhibition of mitochondrial membrane potential disruption and cytochrome c release in RINm5F (RIN) rat insulinoma cells. In this study, the preventive effects of CRE against cytokine-induced β-cell death was assessed. Cytokines generated by immune cells infiltrating pancreatic islets are crucial mediators of β-cell destruction in insulin-dependent diabetes mellitus. The treatment of RIN cells with IL-1β and IFN-γ resulted in a reduction of cell viability. CRE completely protected IL-1β and IFN-γ-mediated cell death in a concentration-dependent manner. Incubation with CRE induced a significant suppression of IL-1β and IFN-γ-induced nitric oxide (NO) production, a finding which correlated well with reduced levels of the iNOS mRNA and protein. The molecular mechanism by which CRE inhibited iNOS gene expression appeared to involve the inhibition of NF-κB activation. The IL-1β and IFN-γ-stimulated RIN cells showed increases in NF-κB binding activity and p65 subunit levels in nucleus, and IκBα degradation in cytosol compared to unstimulated cells. Furthermore, the protective effects of CRE were verified via the observation of reduced NO generation and iNOS expression, and normal insulin-secretion responses to glucose in IL-1β and IFN-γ-treated islets.

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Section: Discussionmentioning

confidence: 99%

Coptidis rhizoma extract protects against cytokine-induced death of pancreatic β-cells through suppression of NF-κ B activation

Kim

Kwon²,

Han³

et al. 2007

Exp Mol Med

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“…4,5 One candidate gene targeted by NF-kB is the enzyme cyclooxygenase-2 (COX-2) whose activity, along with that of microsomal PGES-1 (mPGES-1), is necessary for the synthesis of PGE 2 during inflammation. [6][7][8][9] However, the promoter of mPGES-1 gene does not contain NF-kB consensus sequences, and instead AP-1 and early growth response-1 appear to be critical for mPGES-1 expression. 10 Although COX-2 and mPGES-1 transcriptional activation takes place in cells of the BBB in various models of systemic inflammation, 4,11 the main cell type expressing these transcripts and producing PGE 2 is still under debate.…”

Section: Introductionmentioning

confidence: 99%

MyD88 signaling in brain endothelial cells is essential for the neuronal activity and glucocorticoid release during systemic inflammation

Gosselin

Rivest

2008

Mol Psychiatry

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Activation of neuronal circuits involved in the control of autonomic responses is critical for the host survival to immune threats. The brain vascular system plays a key role in such immune-CNS communication, but the signaling pathway and exact type of cells within the blood-brain barrier (BBB) mediating these functions have yet to be uncovered. To elucidate this issue we used myeloid differentiation factor 88 (MyD88)-deficient mice, because these animals do not show any responses to the cytokine interleukin-1b (IL-1b). We created chimeric mice with competent MyD88 signaling in either the BBB endothelium or perivascular microglia of bone marrow origin and challenged them with IL-1b. Systemic treatment with the cytokine caused a robust transcriptional activation of genes involved in the prostaglandin E 2 (PGE 2 ) production by vascular cells of the brain. Upregulation of these genes is dependent on a functional MyD88 signaling in the endothelium, because MyD88-deficient mice that received bone marrow stem cells from wild-type animals (for example, functional perivascular microglia) exhibited no response to systemic IL-1b administration. MyD88 competent endothelial cells also mediate neuronal activation and plasma release of glucocorticoids, whereas chimeric mice with MyD88-competent perivascular microglia did not show a significant increase of these functions. Moreover, competent endothelial cells for the gene encoding Toll-like receptor 4 (TLR4) are essential for the release of plasma corticosterone in response to low and high doses of lipopolysaccharide. Therefore, BBB endothelial cells and not perivascular microglia are the main target of circulating inflammatory mediators to activate the brain circuits and key autonomic functions during systemic immune challenges.

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“…19,20 The binding of IL-1␤ to its cognate type I receptor leads to the formation of the IL-1 receptor-associated kinases (IRAK)/TNF receptor-associated factor 6 (TRAF6)/ACP complex, which activates NIK/IKK kinases involved in the phosphorylation and degradation of I B␣. 16 NF-B is then translocated into the nucleus and may bind to Figure 1 Phenotype of COX-2-and I B␣-expressing cells in a rat cerebral blood vessel (bv) during systemic inflammatory insults.…”

Section: The Nk-b Storymentioning

confidence: 99%

“…17 Two putative NF-B motifs from the COX-2 promoter were found to bind p50/p65 NF-B heterodimers in an IL-1␤-dependent manner and the two NF-B subunits synergistically activate a −917/+49 COX-2 promoter construct. 19,20 Like IL-1␤, i.v. TNF-␣ injection causes a robust and transient transcriptional activation of I B␣ and COX-2 in endothelial cells lining the CNS vascular system.…”

Section: The Nk-b Storymentioning

confidence: 99%

What is the cellular source of prostaglandins in the brain in response to systemic inflammation? Facts and controversies

Rivest

1999

Mol Psychiatry

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Circulating inflammatory mediators can signal neurons through a pathway in which cytokine activation of the cells of the blood-brain barrier causes the induction of the nuclear factor kappa B (NF-B), leading to the transcription of target genes, such as the one encoding cyclooxygenase 2 (COX-2), the enzyme that initiates prostaglandin formation. These active products of the arachidonate metabolism produced by the cerebral microvasculature have critical roles in initiating the neuronal responses and the neurophysiological outcomes that take place during immunogenic stimuli, including sickness behaviors, fever and increase in the hypothalamic-pituitary adrenal axis. Whether there is more than a single cell type in the blood-brain barrier responsible for the synthesis of prostanoids in the presence of circulating proinflammatory cytokines is an interesting debate that will be summarized here.

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Basal expression of cyclooxygenase-2 and nuclear factor–interleukin 6 are dominant and coordinately regulated by interleukin 1 in the pancreatic islet

Cited by 138 publications

References 43 publications

Coptidis rhizoma extract protects against cytokine-induced death of pancreatic β-cells through suppression of NF-κ B activation

Coptidis rhizoma extract protects against cytokine-induced death of pancreatic β-cells through suppression of NF-κ B activation

MyD88 signaling in brain endothelial cells is essential for the neuronal activity and glucocorticoid release during systemic inflammation

What is the cellular source of prostaglandins in the brain in response to systemic inflammation? Facts and controversies

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