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NEMO prevents RIP kinase 1-mediated epithelial cell death and chronic intestinal inflammation by NF-κB-dependent and -independent functions

(2016) IMMUNITY. 44(3). p.553-567
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Abstract
Intestinal epithelial cells (IECs) regulate gut immune homeostasis, and impaired epithelial responses are implicated in the pathogenesis of inflammatory bowel diseases (IBD). IEC-specific ablation of nuclear factor kappa B (NF-kappa B) essential modulator (NEMO) caused Paneth cell apoptosis and impaired antimicrobial factor expression in the ileum, as well as colonocyte apoptosis and microbiota-driven chronic inflammation in the colon. Combined RelA, c-Rel, and RelB deficiency in IECs caused Paneth cell apoptosis but not colitis, suggesting that NEMO prevents colon inflammation by NF-kappa B-independent functions. Inhibition of receptor-interacting protein kinase 1 (RIPK1) kinase activity or combined deficiency of Fas-associated via death domain protein (FADD) and RIPK3 prevented epithelial cell death, Paneth cell loss, and colitis development in mice with epithelial NEMO deficiency. Therefore, NEMO prevents intestinal inflammation by inhibiting RIPK1 kinase activity-mediated IEC death, suggesting that RIPK1 inhibitors could be effective in the treatment of colitis in patients with NEMO mutations and possibly in IBD.
Keywords
NLRP3 INFLAMMASOME, ANHIDROTIC ECTODERMAL DYSPLASIA, BOWEL-DISEASE, IKK-BETA, HOMEOSTASIS, APOPTOSIS, NECROPTOSIS, ACTIVATION, EXPRESSION, IMMUNITY

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MLA
Vlantis, Katerina, et al. “NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-ΚB-Dependent and -Independent Functions.” IMMUNITY, vol. 44, no. 3, 2016, pp. 553–67, doi:10.1016/j.immuni.2016.02.020.
APA
Vlantis, K., Wullaert, A., Polykratis, A., Kondylis, V., Dannappel, M., Schwarzer, R., … Pasparakis, M. (2016). NEMO prevents RIP kinase 1-mediated epithelial cell death and chronic intestinal inflammation by NF-κB-dependent and -independent functions. IMMUNITY, 44(3), 553–567. https://doi.org/10.1016/j.immuni.2016.02.020
Chicago author-date
Vlantis, Katerina, Andy Wullaert, Apostolos Polykratis, Vangelis Kondylis, Marius Dannappel, Robin Schwarzer, Patrick Welz, et al. 2016. “NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-ΚB-Dependent and -Independent Functions.” IMMUNITY 44 (3): 553–67. https://doi.org/10.1016/j.immuni.2016.02.020.
Chicago author-date (all authors)
Vlantis, Katerina, Andy Wullaert, Apostolos Polykratis, Vangelis Kondylis, Marius Dannappel, Robin Schwarzer, Patrick Welz, Teresa Corona, Henning Walczak, Falk Weih, Ulf Klein, Michelle Kelliher, and Manolis Pasparakis. 2016. “NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-ΚB-Dependent and -Independent Functions.” IMMUNITY 44 (3): 553–567. doi:10.1016/j.immuni.2016.02.020.
Vancouver
1.
Vlantis K, Wullaert A, Polykratis A, Kondylis V, Dannappel M, Schwarzer R, et al. NEMO prevents RIP kinase 1-mediated epithelial cell death and chronic intestinal inflammation by NF-κB-dependent and -independent functions. IMMUNITY. 2016;44(3):553–67.
IEEE
[1]
K. Vlantis et al., “NEMO prevents RIP kinase 1-mediated epithelial cell death and chronic intestinal inflammation by NF-κB-dependent and -independent functions,” IMMUNITY, vol. 44, no. 3, pp. 553–567, 2016.
@article{8070618,
  abstract     = {{Intestinal epithelial cells (IECs) regulate gut immune homeostasis, and impaired epithelial responses are implicated in the pathogenesis of inflammatory bowel diseases (IBD). IEC-specific ablation of nuclear factor kappa B (NF-kappa B) essential modulator (NEMO) caused Paneth cell apoptosis and impaired antimicrobial factor expression in the ileum, as well as colonocyte apoptosis and microbiota-driven chronic inflammation in the colon. Combined RelA, c-Rel, and RelB deficiency in IECs caused Paneth cell apoptosis but not colitis, suggesting that NEMO prevents colon inflammation by NF-kappa B-independent functions. Inhibition of receptor-interacting protein kinase 1 (RIPK1) kinase activity or combined deficiency of Fas-associated via death domain protein (FADD) and RIPK3 prevented epithelial cell death, Paneth cell loss, and colitis development in mice with epithelial NEMO deficiency. Therefore, NEMO prevents intestinal inflammation by inhibiting RIPK1 kinase activity-mediated IEC death, suggesting that RIPK1 inhibitors could be effective in the treatment of colitis in patients with NEMO mutations and possibly in IBD.}},
  author       = {{Vlantis, Katerina and Wullaert, Andy and Polykratis, Apostolos and Kondylis, Vangelis and Dannappel, Marius and Schwarzer, Robin and Welz, Patrick and Corona, Teresa and Walczak, Henning and Weih, Falk and Klein, Ulf and Kelliher, Michelle and Pasparakis, Manolis}},
  issn         = {{1074-7613}},
  journal      = {{IMMUNITY}},
  keywords     = {{NLRP3 INFLAMMASOME,ANHIDROTIC ECTODERMAL DYSPLASIA,BOWEL-DISEASE,IKK-BETA,HOMEOSTASIS,APOPTOSIS,NECROPTOSIS,ACTIVATION,EXPRESSION,IMMUNITY}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{553--567}},
  title        = {{NEMO prevents RIP kinase 1-mediated epithelial cell death and chronic intestinal inflammation by NF-κB-dependent and -independent functions}},
  url          = {{http://doi.org/10.1016/j.immuni.2016.02.020}},
  volume       = {{44}},
  year         = {{2016}},
}

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