Enterotoxigenic Bacteroides fragilis activates IL-8 expression through Stat3 in colorectal cancer cells

Abstract Background Enterotoxigenic Bacteroides fragilis (ETBF) has been implicated in colorectal carcinogenesis through the actions of its toxin, B. fragilis toxin (BFT). Studies on colorectal cell lines have shown that treatment with BFT causes disruption of E-cadherin leading to increased express...

Full description

Bibliographic Details
Main Authors: Rachel V. Purcell, Jessica Permain, Jacqueline I. Keenan
Format: Article
Language:English
Published: BMC 2022-04-01
Series:Gut Pathogens
Subjects:
Online Access:https://doi.org/10.1186/s13099-022-00489-x
_version_ 1828839840229097472
author Rachel V. Purcell
Jessica Permain
Jacqueline I. Keenan
author_facet Rachel V. Purcell
Jessica Permain
Jacqueline I. Keenan
author_sort Rachel V. Purcell
collection DOAJ
description Abstract Background Enterotoxigenic Bacteroides fragilis (ETBF) has been implicated in colorectal carcinogenesis through the actions of its toxin, B. fragilis toxin (BFT). Studies on colorectal cell lines have shown that treatment with BFT causes disruption of E-cadherin leading to increased expression of the pro-inflammatory cytokine, IL-8. Stat3 activation has also been associated with ETBF-related colitis and tumour development. However, a link between E-cadherin, IL-8 and Stat3 has not been investigated in the context of ETBF infection. Results We found that co-culture of HT-29 and HCT116 colorectal cell lines with ETBF, had a similar effect on activation of IL8 gene and protein expression as treatment with purified BFT. Inhibition of Stat3 resulted in a decrease in IL-8 gene and protein expression in response to ETBF in both cell lines. A reduction in E-cadherin expression in response to ETBF treatment was not restored by blocking Stat3. Conclusion We found that treatment of colorectal cancer cell lines with live cultures of ETBF had the equivalent effect on IL-8 expression as the use of purified toxin, and this may be a more representative model of ETBF-mediated colorectal carcinogenesis. IL-8 gene and protein expression was mediated through Stat3 in HT-29 and HCT116 cells, whereas disruption of E-cadherin appeared to be independent of Stat3 signalling.
first_indexed 2024-12-12T19:31:34Z
format Article
id doaj.art-20c18d3aa6cb448895b13ab03cf74638
institution Directory Open Access Journal
issn 1757-4749
language English
last_indexed 2024-12-12T19:31:34Z
publishDate 2022-04-01
publisher BMC
record_format Article
series Gut Pathogens
spelling doaj.art-20c18d3aa6cb448895b13ab03cf746382022-12-22T00:14:25ZengBMCGut Pathogens1757-47492022-04-011411710.1186/s13099-022-00489-xEnterotoxigenic Bacteroides fragilis activates IL-8 expression through Stat3 in colorectal cancer cellsRachel V. Purcell0Jessica Permain1Jacqueline I. Keenan2Department of Surgery, University of OtagoDepartment of Surgery, University of OtagoDepartment of Surgery, University of OtagoAbstract Background Enterotoxigenic Bacteroides fragilis (ETBF) has been implicated in colorectal carcinogenesis through the actions of its toxin, B. fragilis toxin (BFT). Studies on colorectal cell lines have shown that treatment with BFT causes disruption of E-cadherin leading to increased expression of the pro-inflammatory cytokine, IL-8. Stat3 activation has also been associated with ETBF-related colitis and tumour development. However, a link between E-cadherin, IL-8 and Stat3 has not been investigated in the context of ETBF infection. Results We found that co-culture of HT-29 and HCT116 colorectal cell lines with ETBF, had a similar effect on activation of IL8 gene and protein expression as treatment with purified BFT. Inhibition of Stat3 resulted in a decrease in IL-8 gene and protein expression in response to ETBF in both cell lines. A reduction in E-cadherin expression in response to ETBF treatment was not restored by blocking Stat3. Conclusion We found that treatment of colorectal cancer cell lines with live cultures of ETBF had the equivalent effect on IL-8 expression as the use of purified toxin, and this may be a more representative model of ETBF-mediated colorectal carcinogenesis. IL-8 gene and protein expression was mediated through Stat3 in HT-29 and HCT116 cells, whereas disruption of E-cadherin appeared to be independent of Stat3 signalling.https://doi.org/10.1186/s13099-022-00489-xEnterotoxigenic Bacteroides fragilisToxinInterleukin-8IL-8Stat3E-cadherin
spellingShingle Rachel V. Purcell
Jessica Permain
Jacqueline I. Keenan
Enterotoxigenic Bacteroides fragilis activates IL-8 expression through Stat3 in colorectal cancer cells
Gut Pathogens
Enterotoxigenic Bacteroides fragilis
Toxin
Interleukin-8
IL-8
Stat3
E-cadherin
title Enterotoxigenic Bacteroides fragilis activates IL-8 expression through Stat3 in colorectal cancer cells
title_full Enterotoxigenic Bacteroides fragilis activates IL-8 expression through Stat3 in colorectal cancer cells
title_fullStr Enterotoxigenic Bacteroides fragilis activates IL-8 expression through Stat3 in colorectal cancer cells
title_full_unstemmed Enterotoxigenic Bacteroides fragilis activates IL-8 expression through Stat3 in colorectal cancer cells
title_short Enterotoxigenic Bacteroides fragilis activates IL-8 expression through Stat3 in colorectal cancer cells
title_sort enterotoxigenic bacteroides fragilis activates il 8 expression through stat3 in colorectal cancer cells
topic Enterotoxigenic Bacteroides fragilis
Toxin
Interleukin-8
IL-8
Stat3
E-cadherin
url https://doi.org/10.1186/s13099-022-00489-x
work_keys_str_mv AT rachelvpurcell enterotoxigenicbacteroidesfragilisactivatesil8expressionthroughstat3incolorectalcancercells
AT jessicapermain enterotoxigenicbacteroidesfragilisactivatesil8expressionthroughstat3incolorectalcancercells
AT jacquelineikeenan enterotoxigenicbacteroidesfragilisactivatesil8expressionthroughstat3incolorectalcancercells