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NF-kappa Bp65 and expression of its pro-inflammatory target genes are upregulated in the subcutaneous adipose tissue of cachectic cancer patients

  • Cancer cachexia, of which the most notable symptom is severe and rapid weight loss, is present in the majority of patients with advanced cancer. Inflammatory mediators play an important role in the development of cachexia, envisaged as a chronic inflammatory syndrome. The white adipose tissue (WAT) is one of the first compartments affected in cancer cachexia and suffers a high rate of lipolysis. It secretes several cytokines capable of directly regulating intermediate metabolism. A common pathway in the regulation of the expression of pro-inflammatory cytokines in WAT is the activation of the nuclear transcription factor kappa-B (NF-κB). We have examined the gene expression of the subunits NF-κBp65 and NF-κBp50, as well as NF-κBp65 and NF-κBp50 binding, the gene expression of pro-inflammatory mediators under NF-κB control (IL-1β, IL-6, INF-γ, TNF-α, MCP-1), and its inhibitory protein, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκB-α). The observational study involved 35 patients (controlCancer cachexia, of which the most notable symptom is severe and rapid weight loss, is present in the majority of patients with advanced cancer. Inflammatory mediators play an important role in the development of cachexia, envisaged as a chronic inflammatory syndrome. The white adipose tissue (WAT) is one of the first compartments affected in cancer cachexia and suffers a high rate of lipolysis. It secretes several cytokines capable of directly regulating intermediate metabolism. A common pathway in the regulation of the expression of pro-inflammatory cytokines in WAT is the activation of the nuclear transcription factor kappa-B (NF-κB). We have examined the gene expression of the subunits NF-κBp65 and NF-κBp50, as well as NF-κBp65 and NF-κBp50 binding, the gene expression of pro-inflammatory mediators under NF-κB control (IL-1β, IL-6, INF-γ, TNF-α, MCP-1), and its inhibitory protein, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκB-α). The observational study involved 35 patients (control group, n = 12 and cancer group, n = 23, further divided into cachectic and non-cachectic). NF-κBp65 and its target genes expression (TNF-α, IL-1β, MCP-1 and IκB-α) were significantly higher in cachectic cancer patients. Moreover, NF-κBp65 gene expression correlated positively with the expression of its target genes. The results strongly suggest that the NF-κB pathway plays a role in the promotion of WAT inflammation during cachexia.show moreshow less

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Author details:Rodolfo Gonzalez Camargo, Daniela Mendes dos Reis Riccardi, Henrique Quintas Teixeira Ribeiro, Luiz Carlos Carnevali Junior, Emidio Marques de Matos-Neto, Lucas Enjiu, Rodrigo Xavier Neves, Joanna Darck Carola Correia Lima, Raquel Galvão Figuerêdo, Paulo Sérgio Martins de Alcântara, Linda Maximiano, José Otoch, Miguel Luiz Batista Jr., Gerhard Paul PüschelORCiDGND, Marilia Seelaender
URN:urn:nbn:de:kobv:517-opus4-400163
Publication series (Volume number):Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe (349)
Publication type:Postprint
Language:English
Date of first publication:2017/09/15
Publication year:2017
Publishing institution:Universität Potsdam
Release date:2017/09/15
Tag:IκB; NF-κB; cancer cachexia; inflammation; white adipose tissue
Number of pages:15
Source:Nutrients 7 (2015) Nr. 6, S. 4465-4479. - DOI: 10.3390/nu7064465
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft
DDC classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Peer review:Referiert
Publishing method:Open Access
Grantor:Multidisciplinary Digital Publishing Institute (MDPI)
License (German):License LogoCC-BY - Namensnennung 4.0 International
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