Publication Database

Selective role of TNFα and IL10 in regulation of barrier properties of the colon in DMH-induced tumor and healthy rats (2022)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Bekusova, Viktoria

Zudova, Tatiana

Fatyykhov, Ilyas

Fedorova, Arina

Amasheh, Salah (WE 2)

Markov, Alexander G.

Quelle

International journal of molecular sciences

Bandzählung: 23

Heftzählung: 24

Seiten: Artikel 15610

ISSN: 1422-0067

Sprache

Englisch

Verweise

URL (Volltext): https://www.mdpi.com/1422-0067/23/24/15610

DOI: 10.3390/ijms232415610

Kontakt

Institut für Veterinär-Physiologie

Oertzenweg 19 b
14163 Berlin
+49 30 838 62600
physiologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Recently it has been reported that the tumor adjacent colon tissues of 1,2-dymethylhydrazine induced (DMH)-rats revealed a high paracellular permeability. We hypothesized that the changes might be induced by cytokines. Colorectal cancer is accompanied by an increase in tumor necrosis factor alpha (TNFα) and interleukin 10 (IL10) that exert opposite regulatory effects on barrier properties of the colon, which is characterized by morphological and functional segmental heterogeneity. The aim of this study was to analyze the level of TNFα and IL10 in the colon segments of DMH-rats and to investigate their effects on barrier properties of the proximal and distal parts of the colon in healthy rats. Enzyme immunoassay analysis showed decreased TNFα in tumors in the distal part of the colon and increased IL10 in proximal tumors and in non-tumor tissues. Four-hour intraluminal exposure of the colon of healthy rats with cytokines showed reduced colon barrier function dependent on the cytokine: TNFα decreased it mainly in the distal part of the colon, whereas IL10 decreased it only in the proximal part. Western blot analysis revealed a more pronounced influence of IL10 on tight junction (TJ) proteins expression by down-regulation of the TJ proteins claudin-1, -2 and -4, and up-regulation of occludin only in the proximal part of the colon. These data may indicate a selective role of the cytokines in regulation of the barrier properties of the colon and a prominent role of IL10 in carcinogenesis in its proximal part.