5. Protein kinase cascades in intracellular signalling by interleukin-1 and tumour necrosis factor

Saklatvala, Jeremy; Dean, Jon; Finch, Andrew

doi:10.1515/9781400865048.63

Cited by 37 publications

(45 citation statements)

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“…IL-1 and IL-6 regulate each other's expression and are often expressed together at sites of inflammation (2, 3). IL-1 inhibited IL-6-mediated Jak-Stat signaling by a rapidly inducible mechanism, and inhibition of IL-6-induced Stat3 activation was mediated by p38, a kinase that is activated by multiple inflammatory/stress factors and has been strongly implicated in driving inflammation (29,30). Previously described inducible mechanisms of inhibition of Jak-Stat signaling involve synthesis of inhibitory proteins such as SOCS (18 -20, 54), potentially target the Stat molecule itself on a conserved carboxyl-terminal serine (serine 727 in Stat3) (58,60,66), or use the ERK subfamily of MAPKs (37) or PKC␣ or PKC␦ isoforms (67).…”

Section: Discussionmentioning

confidence: 99%

“…IL-1 and TNF activate several signaling pathways, leading to the downstream activation of NF-B transcription factors and activation of c-Jun N-terminal kinases (JNKs) and the p38 kinases (29), collectively termed stress-activated protein kinases (SAPKs), that constitute two subfamilies of mitogen-activated protein kinases (MAPKs) (30). SAPKs are also activated by cellular stressors, including reactive oxygen intermediates, osmolar shock, and UV radiation, some of which are present during inflammation.…”

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confidence: 99%

“…SAPKs are also activated by cellular stressors, including reactive oxygen intermediates, osmolar shock, and UV radiation, some of which are present during inflammation. SAPKs phosphorylate and activate transcription factors, including AP-1, and have been strongly implicated in mediating IL-1 and TNF inflammatory effects (29,30). IL-1 and TNF are expressed at most inflammatory sites, where they regulate the expression of other cytokines and interact with other immune/inflammatory cytokines in a cytokine network (31).…”

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confidence: 99%

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Inhibition of IL-6 and IL-10 Signaling and Stat Activation by Inflammatory and Stress Pathways

Ahmed¹,

Ivashkiv

2000

The Journal of Immunology

120

110

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The development and resolution of an inflammatory process are regulated by a complex interplay among cytokines that have pro- and anti-inflammatory effects. Effective and sustained action of a proinflammatory cytokine depends on synergy with other inflammatory cytokines and antagonism of opposing cytokines that are often highly expressed at inflammatory sites. We analyzed the effects of the inflammatory and stress agents, IL-1, TNF-α, LPS, sorbitol, and H2O2, on signaling by IL-6 and IL-10, pleiotropic cytokines that activate the Jak-Stat signaling pathway and have both pro- and anti-inflammatory actions. IL-1, TNF-α, and LPS blocked the activation of Stat DNA binding and tyrosine phosphorylation by IL-6 and IL-10, but not by IFN-γ, in primary macrophages. Inhibition of Stat activation correlated with inhibition of expression of IL-6-inducible genes. The inhibition was rapid and independent of de novo gene induction and occurred when the expression of suppressor of cytokine synthesis-3 was blocked. Inhibition of IL-6 signaling was mediated by the p38 subfamily of stress-activated protein kinases. Jak1 was inhibited at the level of tyrosine phosphorylation, indicating that inhibition occurred at least in part upstream of Stats in the Jak-Stat pathway. Experiments using Stat3 mutated at serine 727 and using truncated IL-6Rs suggested that the target of inhibition is contained within the membrane-proximal region of the cytoplasmic domain of the gp130 subunit of the IL-6 receptor and is different from the SH2 domain-containing protein-tyrosine phosphatase/suppressor of cytokine synthesis-3 docking site. These results identify a new level at which IL-1 and TNF-α modulate signaling by pleiotropic cytokines such as IL-6 and IL-10 and provide a molecular basis for the previously described antagonism of certain IL-6 actions by IL-1.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Inhibition of IL-6 and IL-10 Signaling and Stat Activation by Inflammatory and Stress Pathways

Ahmed¹,

Ivashkiv

2000

The Journal of Immunology

120

110

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“…38,39 For example, inhibition of p38MAPK by the specific inhibitor SB202190 interferes with stimulatory effects of exogenous TGFb2 on migration of cells and on production of ECM components, such as collagen type I and fibronectin, while having no effects on the basal activity. Moreover, p38 MAPK may affect these end points not only by direct phosphorylation of the Smad proteins in the middle linker region 40 but also TGFb in the eye S Saika by activation of cooperating transcription factors. For example, TGFb-activated kinase (TAK1) has been shown to be an upstream activator of MKK6 and activation of this pathway results in phosphorylation of activating transcription factor 2 (ATF2) and enhancement of complex formation between Smad4 and ATF2.…”

Section: Tgfb Signal Transductionmentioning

confidence: 99%

TGFβ pathobiology in the eye

Saika

2006

Laboratory Investigation

240

185

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“…This is also related to apoptosis and antiapoptosis, and is activated by cytokines or stress stimuli such as osmotic shock, UV light, and heat [9,18] . IGF-Ⅰ system has been reported to protect against a variety of chemical cellular injuries that induce apoptosis [19] .…”

Section: Discussionmentioning

confidence: 99%

Effects of ethanol on insulin-like growth factor-I system in primary cultured rat hepatocytes: Implications of JNK1/2 and alcoholdehydrogenase

Kim²,

Kang³

2008

WJG

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AIM:To evaluate the effects of ethanol on the insulinlike growth factor-Ⅰ (IGF-Ⅰ) system involved in c-Jun N-terminal kinase (JNK1/2) and alcoholdehydrogenase (ADH) activity in primary cultured rat hepatocytes. M E T H O D S : H e p a t o c y t e s i s o l a t e d f r o m m a l eSprague-Dawley rats were incubated with various concentrations of ethanol for different durations of time. The cells were pretreated with SP600125 (10 μmol/L) and 4-MP (200 μmol/L), and then treated with ethanol (200 mmol/L). We then measured IGF-Ⅰ secretion, IGF-Ⅰ mRNA expression, cell viability and JNK1/2 activity by radioimmunoassay, RT-PCR, MTT assay and Western blot, respectively (n = 6). RESULTS: Ethanol induced the activity of phospho (p)-JNK1/2, reaching a maximum at 60 min and then decreasing at 180 min. The effects of ethanol on the IGF-Ⅰ system were increased at 60 min (secretion:7.11 ± 0.59 ng/mg protein vs 4.91 ± 0.51 ng/mg, mRNA expression: 150.2% ± 10.2% vs 101.5% ± 11.3%, P = 0.045) and then decreased at 180 min (secretion: 3.89 ± 0.25 ng/mg vs 5.4 ± 0.54 ng/mg protein; mRNA expression: 41.5% ± 10.4% vs 84.7% ± 12.1%, P = 0.04), however cell viability was decreased in a dose-and time-dependent manner. SP600125 blocked the ethanol-induced changes (at 60 min). Additionally, 4-methylpyrazole prevented the ethanol-induced decreases in the IGF-Ⅰ system, cell viability and p-JNK1/2 activity (at 180 min). CONCLUSION: This study suggests that ethanolinduced p-JNK1/2 activation is associated with the IGF-Ⅰ system and cell viability in hepatocytes. Furthermore, alcohol dehydrogenase is involved in the relationship between ethanol-induced inactivation of p-JNK1/2 and the changes of the IGF-Ⅰ system and cell viability. Oh YI, Kim JH, Kang CW. Effects of ethanol on insulin-like growth factor-Ⅰ system in primary cultured rat hepatocytes: Implications of JNK1/2 and alcoholdehydrogenase.

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5. Protein kinase cascades in intracellular signalling by interleukin-1 and tumour necrosis factor

Cited by 37 publications

References 0 publications

Inhibition of IL-6 and IL-10 Signaling and Stat Activation by Inflammatory and Stress Pathways

Inhibition of IL-6 and IL-10 Signaling and Stat Activation by Inflammatory and Stress Pathways

TGFβ pathobiology in the eye

Effects of ethanol on insulin-like growth factor-I system in primary cultured rat hepatocytes: Implications of JNK1/2 and alcoholdehydrogenase

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