CARMA3/Bcl10/MALT1-dependent NF-κB activation mediates angiotensin II-responsive inflammatory signaling in nonimmune cells

McAllister-Lucas, Linda M.; Ruland, Jürgen; Siu, Katy; Jin, Xiaohong; Gu, Shufang; Kim, David S.L.; Kuffa, Peter; Kohrt, Dawn; Mak, Tak W.; Núñez, Gabriel; Lucas, Peter C.

doi:10.1073/pnas.0601947103

Cited by 160 publications

(167 citation statements)

References 55 publications

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“…Similar defect is observed following stimulation with other GPCR ligands, such as endothelin-1 and angiotensin-II, in the absence of CARMA3 [123,128,129]. Importantly, CARMA3 is specifically required for GP-CR-induced IKK activity because CARMA3 deficiency does not affect IKK activation by other stimuli such as TNFα and lipopolysaccharide (LPS) [123].…”

Section: Carma3-mediated Nf-κb Signaling Pathwaysmentioning

confidence: 56%

NF-κB signaling pathways regulated by CARMA family of scaffold proteins

Blonska¹,

Lin²

2010

Cell Res

176

201

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The NF-κB family of transcription factors plays a crucial role in cell activation, survival and proliferation. Its aberrant activity results in cancer, immunodeficiency or autoimmune disorders. Over the past two decades, tremendous progress has been made in our understanding of the signals that regulate NF-κB activation, especially how scaffold proteins link different receptors to the NF-κB-activating complex, the IκB kinase complex. The growing number of these scaffolds underscores the complexity of the signaling networks in different cell types. In this review, we discuss the role of scaffold molecules in signaling cascades induced by stimulation of antigen receptors, G-protein-coupled receptors and C-type Lectin receptors, resulting in NF-κB activation. Especially, we focus on the family of Caspase recruitment domain (CARD)-containing proteins known as CARMA and their function in activation of NF-κB, as well as the link of these scaffolds to the development of various neoplastic diseases through regulation of NF-κB.

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Section: Carma3-mediated Nf-κb Signaling Pathwaysmentioning

confidence: 56%

NF-κB signaling pathways regulated by CARMA family of scaffold proteins

Blonska¹,

Lin²

2010

Cell Res

176

201

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“…Recent reports, including our work in human colonic epithelial cells, have also established a role for Bcl10 in an inflammatory pathway in non-immune cells, including mouse embryonic kidney cells and hepatocytes [5,8,[20][21][22]. Bcl10 is recognized as a mediator of constitutive activation of NFκB in the MALT lymphomas, in which there is a translocation involving Bcl10 [23][24][25].…”

Section: Discussionmentioning

confidence: 99%

Carrageenan-induced NFκB activation depends on distinct pathways mediated by reactive oxygen species and Hsp27 or by Bcl10

Bhattacharyya

Dudeja

Tobacman

2008

Biochimica et Biophysica Acta (BBA) - General Subjects

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Carrageenans are highly sulfated polysaccharides that are widely used as food additives due to their ability to improve food texture. They are also widely recognized for their ability to induce inflammation in animal models of colitis. Recently, we reported that carrageenan (CGN) activated a pathway of innate immunity in human colonic epithelial cells mediated by Bcl10 (B-cell CLL/ lymphoma 10). However, increases in phospho-IκBα and Interleukin-8 (IL-8) were not completely inhibited by silencing Bcl10, suggesting that CGN also influenced another mechanism, or mechanisms, of inflammation. In this report, we demonstrate that CGN increases production of reactive oxygen species (ROS) in human colonic epithelial cells. The combination of ROS quenching by the free radical scavenger Tempol and of Bcl10 silencing by siRNA completely inhibited the CGN-induced increases in nuclear NFκB (p65), phospho-IκBα, and secretion of IL-8. The CGN-induced increase in ROS was associated with declines in phosphorylation of MAPK 12 (p38γ), MAPK 13 (p38δ), and heat-shock protein (Hsp) 27. The CGN-induced decline in phospho-Hsp27 was reversed by co-administration of Tempol (100nM), but unaffected by silencing Bcl10. Since Hsp27 phosphorylation is inversely associated with phosphorylation of the IκBα kinase (IKK) signalosome, CGN exposure appears to affect the IKK signalosome by both the catalytic component, mediated by ROS-phospho-Hsp27, and the regulatory component, mediated by Bcl10 interaction with IKKγ (Nemo). Hence, the CGN-activated inflammatory cascades related to innate immunity and to generation of ROS may be integrated at the level of the IKK signalosome.

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“…A continuous activation was detected at low levels after PH while a delayed and more pronounced activation could be seen after SH. While basal activation of NF-κB may be sufficient and important for regeneration and structural reformation after 70% resection [29] , the strong NF-κB activation in animals with 90% hepatectomy may also favor inflammatory processes in the damaged tissue, which counteract the restoration of a functional liver [21,30,31] .…”

Section: Discussionmentioning

confidence: 99%

Extent of liver resection modulates the activation of transcription factors and the production of cytokines involved in liver regeneration

Sowa¹,

Best²,

Benkő³

et al. 2008

WJG

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AIM:To investigate the molecular events involved in liver regeneration following subtotal hepatectomy (SH) as previous studies have largely focused on partial hepatectomy (PH). METHODS:Male Wistar rats were subjected to 70% PH or 90% SH, respectively, and sacrificed at different times after surgery. Untreated and sham-operated animals served as controls. Serum and liver samples were obtained to investigate liver function, apoptosis (TUNEL assay) and transcription factors (NF-κB, Stat3; ELISA) or cytokines (HGF, TNF-a, IL-6, TGF-a, TGF-b; quantitative RT-PCR) involved in liver regeneration. RESULTS:Serum levels of ALT and AST in animals with 70% PH differed significantly from sham-operated and control animals. We found that the peak concentration 12 h after surgery returned to control levels 7 d after surgery. LDH was increased only at 12 h after 70% PH compared to sham. Bilirubin showed no differences between the sham and 70% resection. After PH, early NF-κB activation was detected 12 h after surgery (313.21 ± 17.22 ng/mL), while there was no activation after SH (125.22 ± 44.36 ng/mL) compared to controls (111.43 ± 32.68 ng/mL) at this time point. In SH, however, NF-κB activation was delayed until 24 h (475.56 ± 144.29 ng/mL). Stat3 activation was similar in both groups. These findings correlated with suppressed and delayed induction of regenerative genes after SH (i.e. TNF-a 24 h postoperatively: 2375 ± 1220 in 70% and 88 ± 31 in 90%; IL-6 12 h postoperatively: 2547 ± 441 in 70% and 173 ± 82 in 90%). TUNEL staining revealed elevated apoptosis rates in SH (0.44% at 24 h; 0.63% at 7 d) compared to PH (0.27% at 24 h; 0.15% at 7 d). CONCLUSION:The molecular events involved in liver regeneration are significantly influenced by the extent of resection as SH leads to suppression and delay of liver regeneration compared to PH, which is associated with delayed activation of NF-κB and suppression of proregenerative cytokines.

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CARMA3/Bcl10/MALT1-dependent NF-κB activation mediates angiotensin II-responsive inflammatory signaling in nonimmune cells

Cited by 160 publications

References 55 publications

NF-κB signaling pathways regulated by CARMA family of scaffold proteins

NF-κB signaling pathways regulated by CARMA family of scaffold proteins

Carrageenan-induced NFκB activation depends on distinct pathways mediated by reactive oxygen species and Hsp27 or by Bcl10

Extent of liver resection modulates the activation of transcription factors and the production of cytokines involved in liver regeneration

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