scholarly journals Resveratrol Attenuates Microglial Activation via SIRT1-SOCS1 Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Shuping Zhang ◽  
Lu Gao ◽  
Xiuying Liu ◽  
Tao Lu ◽  
Chuangbo Xie ◽  
...  
Keyword(s):  
Microglial Activation ◽  
Interleukin 1 ◽  
Underlying Mechanism ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Neuron Death ◽  
Related Enzyme ◽  
Oxide Synthase ◽  
Interfering Rna ◽  
Proinflammatory Factors

Microglial activation is involved in a variety of neurological disorders, and overactivated microglial cells can secrete large amount of proinflammatory factors and induce neuron death. Therefore, reducing microglial activation is believed to be useful in treating the disorders. In this study, we used 10 ng/ml lipopolysaccharide plus 10 U/ml interferon γ (LPS/IFNγ) to induce N9 microglial activation and explored resveratrol- (RSV-) induced effects on microglial activation and the underlying mechanism. We found that LPS/IFNγ exposure for 24 h increased inducible nitric oxide synthase (iNOS) and nuclear factor κB (NF-κB) p65 subunit expressions in the cells and enhanced tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) releases from the cells. RSV of 25 μM reduced the iNOS and NF-κB p65 subunit expressions and the proinflammatory factors’ releases; the knockdown of silent information regulator factor 2-related enzyme 1 (SIRT1) or suppressor of cytokine signaling 1 (SOCS1) by using the small interfering RNA, however, significantly abolished the RSV-induced effects on iNOS and NF-κB p65 subunit expressions and the proinflammatory factors’ releases. These findings showed that microglial SIRT1-SOCS1 pathway may mediate the RSV-induced inhibition of microglial activation in the LPS/IFNγ-treated N9 microglia.

scholarly journals Suppressor of Cytokine Signaling-3 Inhibits Interleukin-1 Signaling by Targeting the TRAF-6/TAK1 Complex

2006 ◽  
Vol 20 (7) ◽  
pp. 1587-1596 ◽  
Author(s):  
Helle Frobøse ◽  
Sif Groth Rønn ◽  
Peter E. Heding ◽  
Heidi Mendoza ◽  
Philip Cohen ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Interleukin 1 ◽  
Cytokine Signaling ◽  
Nuclear Factor ◽  
Tnf Receptor ◽  
Suppressor Of Cytokine Signaling ◽  
Signaling Complex ◽  
Nuclear Factor Κ B ◽  
Erk Kinase

Abstract IL-1 plays a major role in inflammation and autoimmunity through activation of nuclear factor κ B (NFκB) and MAPKs. Although a great deal is known about the mechanism of activation of NFκB and MAPKs by IL-1, much less is known about the down-regulation of this pathway. Suppressor of cytokine signaling (SOCS)-3 was shown to inhibit IL-1-induced transcription and activation of NFκB and the MAPKs JNK and p38, but the mechanism is unknown. We show here that SOCS-3 inhibits NFκB-dependent transcription induced by overexpression of the upstream IL-1 signaling molecules MyD88, IL-1R-activated kinase 1, TNF receptor-associated factor (TRAF)6, and TGFβ-activated kinase (TAK)1, but not when the MAP3K MAPK/ERK kinase kinase-1 is used instead of TAK1, indicating that the target for SOCS-3 is the TRAF6/TAK1 signaling complex. By coimmunoprecipitation, it was shown that SOCS-3 inhibited the association between TRAF6 and TAK1 and that SOCS-3 coimmunoprecipitated with TAK1 and TRAF6. Furthermore, SOCS-3 inhibited the IL-1-induced catalytic activity of TAK1. Because ubiquitination of TRAF6 is required for activation of TAK1, we analyzed the role of SOCS-3 on TRAF6 ubiquitination and found that SOCS-3 inhibited ubiquitin modification of TRAF6. These results indicate that SOCS-3 inhibits IL-1 signal transduction by inhibiting ubiquitination of TRAF6, thus preventing association and activation of TAK1.

scholarly journals Suppressor of cytokine signaling 3 (SOCS-3) protects  -cells against interleukin-1 - and interferon- -mediated toxicity

2001 ◽  
Vol 98 (21) ◽  
pp. 12191-12196 ◽  
Author(s):  
A. E. Karlsen ◽  
S. G. Ronn ◽  
K. Lindberg ◽  
J. Johannesen ◽  
E. D. Galsgaard ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling

scholarly journals IFNγ-dependent, spontaneous development of colorectal carcinomas in SOCS1-deficient mice

2006 ◽  
Vol 203 (6) ◽  
pp. 1391-1397 ◽  
Author(s):  
Toshikatsu Hanada ◽  
Takashi Kobayashi ◽  
Takatoshi Chinen ◽  
Kazuko Saeki ◽  
Hiromi Takaki ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Tumor Development ◽  
Cytokine Signaling ◽  
Colorectal Carcinomas ◽  
Suppressor Of Cytokine Signaling ◽  
Human Cancers ◽  
Oxide Synthase ◽  
Deficient Mice ◽  
Inducible Nitric Oxide

Approximately 20% of human cancers are estimated to develop from chronic inflammation. Recently, the NF-κB pathway was shown to play an essential role in promoting inflammation-associated cancer, but the role of the JAK/STAT pathway, another important signaling pathway of proinflammatory cytokines, remains to be investigated. Suppressor of cytokine signaling-1 (SOCS1) acts as an important physiological regulator of cytokine responses, and silencing of the SOCS1 gene by DNA methylation has been found in several human cancers. Here, we demonstrated that SOCS1-deficient mice (SOCS1−/−Tg mice), in which SOCS1 expression was restored in T and B cells on a SOCS1−/− background, spontaneously developed colorectal carcinomas carrying nuclear β-catenin accumulation and p53 mutations at 6 months of age. However, interferon (IFN)γ−/−SOCS1−/− mice and SOCS1−/−Tg mice treated with anti-IFNγ antibody did not develop such tumors. STAT3 and NF-κB activation was evident in SOCS1−/−Tg mice, but these were not sufficient for tumor development because these are also activated in IFNγ−/−SOCS1−/− mice. However, colons of SOCS1−/−Tg mice, but not IFNγ−/−SOCS1−/− mice, showed hyperactivation of STAT1, which resulted in the induction of carcinogenesis-related enzymes, cyclooxygenase-2 and inducible nitric oxide synthase. These data strongly suggest that SOCS1 is a unique antioncogene which prevents chronic inflammation-mediated carcinogenesis by regulation of the IFNγ/STAT1 pathways.

scholarly journals Early Postnatal Hyperalimentation Impairs Renal Function via SOCS-3 Mediated Renal Postreceptor Leptin Resistance

Endocrinology ◽  
2012 ◽  
Vol 153 (3) ◽  
pp. 1397-1410 ◽  
Author(s):  
Miguel Angel Alejandre Alcazar ◽  
Eva Boehler ◽  
Eva Rother ◽  
Kerstin Amann ◽  
Christina Vohlen ◽  
...  
Keyword(s):  
Renal Function ◽  
Underlying Mechanism ◽  
Male Rats ◽  
Leptin Resistance ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Control Male ◽  
Extracellular Matrix Molecules ◽  
And Function

Early postnatal hyperalimentation has long-term implications for obesity and developing renal disease. Suppressor of cytokine signaling (SOCS) 3 inhibits phosphorylation of signal transducer and activator of transcription (STAT) 3 and ERK1/2 and thereby plays a pivotal role in mediating leptin resistance. In addition, SOCS-3 is induced by both leptin and inflammatory cytokines. However, little is known about the intrinsic-renal leptin synthesis and function. Therefore, this study aimed to elucidate the implications of early postnatal hyperalimentation on renal function and on the intrinsic-renal leptin signaling. Early postnatal hyperalimentation in Wistar rats during lactation was induced by litter size reduction at birth (LSR) either to LSR10 or LSR6, compared with home cage control male rats. Assessment of renal function at postnatal day 70 revealed decreased glomerular filtration rate and proteinuria after LSR6. In line with this impairment of renal function, renal inflammation and expression as well as deposition of extracellular matrix molecules, such as collagen I, were increased. Furthermore, renal expression of leptin and IL-6 was up-regulated subsequent to LSR6. Interestingly, the phosphorylation of Stat3 and ERK1/2 in the kidney, however, was decreased after LSR6, indicating postreceptor leptin resistance. In accordance, neuropeptide Y (NPY) gene expression was down-regulated; moreover, SOCS-3 protein expression, a mediator of postreceptor leptin resistance, was strongly elevated and colocalized with NPY. Thus, our findings not only demonstrate impaired renal function and profibrotic processes but also provide compelling evidence of a SOCS-3-mediated intrinsic renal leptin resistance and concomitant up-regulated NPY expression as an underlying mechanism.

Die Aktivierung der MKK6/p38 Kaskade ist essentiell für die Stabilisierung der Suppressor of Cytokine Signaling 3 mRNA durch TNF-alpha

2006 ◽  
Vol 44 (01) ◽  
Author(s):  
C Ehlting ◽  
F Schaper ◽  
ED Brenndörfer ◽  
PC Heinrich ◽  
D Häussinger ◽  
...  
Keyword(s):  
Tnf Alpha ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling
Sign in / Sign up

Export Citation Format

Share Document