Role of IL-10 in hepatocyte tight junction alteration in mouse model of experimental colitis
Mazzon, E; Puzzolo, D; Caputi, AP; Cuzzocrea, S
HERO ID
1688141
Reference Type
Journal Article
Year
2002
Language
English
PMID
| HERO ID | 1688141 |
|---|---|
| In Press | No |
| Year | 2002 |
| Title | Role of IL-10 in hepatocyte tight junction alteration in mouse model of experimental colitis |
| Authors | Mazzon, E; Puzzolo, D; Caputi, AP; Cuzzocrea, S |
| Journal | Molecular Medicine |
| Volume | 8 |
| Issue | 7 |
| Page Numbers | 353-366 |
| Abstract | Background: A variety of hepatobiliary abnormalities have been described in patients with chronic inflammatory bowel diseases (IBDs). The purpose of this study was to investigate the role of endogenous IL- 10 in alteration of hepatocyte TJ paracellular barrier and in the rapid transcytotic vesicular pathway modification associated with intestinal inflammation. <br> <br>Materials and methods: To address this question, we used an experimental model of colitis, induced by dinitrobenzene sulfonic acid (DNBS). When compared to DNBS-treated IL-10 wild-type (IL-10WT) mice, DNBS-treated IL- 10 knock-out mice (IL- 10KO) mice experienced a higher rate of the extent and severity of the histological signs of colon injury. <br> <br>Results: Colon and liver levels of the pro-inflammatory cytokines tumour necrosis factor, interleukin-1beta,6 and interleukin-6 were also greatly enhanced in IL-10KO mice in comparison to wild-type mice. Liver histology from IL-10KO and IL-10WT did not show any parenchymal and portal tract inflammation at 4 days after DNBS administration. Serum total bilirubin and Alanine aminotransferase, were significantly increased in DNBS-IL-10KO mice vs. DNBS-IL-10KO mice. <br> <br>Therefore, we found an increase of tight junctional permeability to lanthanum nitrate (molecular weight, 433) in the livers from DNBS-treated IL-10WT mice; lanthanum accumulated throughout the junctional area up to the most apical region bordering the lumen. Absence of a functional IL-10 gene in IL-10KO mice resulted in a significant augmentation of apical diffusion of lanthanum after DNBS-induced colitis. Immunofluorescent labelling of frozen liver sections from DNBS-IL-10KO mice, immunolocalization for and claudin-1 and ZO-1 resulted in a significant alteration in the localization of the immunosignals for claudin- I and ZO- I after DNBS administration in comparison with DNBS-IL-10WT. <br> <br>Conclusion: In conclusion, we suggest that the absence of IL-10 may represent an important pathophysiological mechanism of hepatobiliary injuries and cholestasis observed in patients with IBD. |
| Doi | 10.1007/bf03402016 |
| Pmid | 12393933 |
| Wosid | WOS:000178200900003 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Source: Web of Science WOS:000178200900003Scopus URL: https://www.scopus.com/inward/record.uri?eid=2-s2.0-0036431805&doi=10.1007%2fbf03402016&partnerID=40&md5=51c7db61e7d0dea19d37b2fb2a741d5a |
| Is Public | Yes |
| Language Text | English |