TITLE:
Bifidobacteria Upregulate Expression of Toll-Like Receptor Negative Regulators Counteracting Enterotoxigenic Escherichia coli Mediated Inflammation in Bovine Intestinal Epitheliocytes
AUTHORS:
Kozue Murata, Julio Villena, Yohsuke Tomosada, Risa Hara, Eriko Chiba, Tomoyuki Shimazu, Hisashi Aso, Yoshihito Suda, Noriyuki Iwabuchi, Jin-Zhong Xiao, Tadao Saito, Haruki Kitazawa
KEYWORDS:
Bovine Intestinal Epithelial Cells; Bifidobacteria; ETEC; TLRs Negative Regulators
JOURNAL NAME:
Open Journal of Veterinary Medicine,
Vol.3 No.2,
June
6,
2013
ABSTRACT:
We previously established a bovine intestinal
epithelial cell line (BIE cells) and showed that BIE cells are useful in
vitro model system for the study of interactions between pathogenic and
beneficial microorganisms and bovine intestinal epithelial cells (IECs). In the
present study, we aimed to
select potential immunomodulatory bifidobacteria that may be used to
beneficially modulate the inflammatory response in bovine IECs. We also aimed
to gain insight into the molecular
mechanisms involved in the anti-inflammatory effect of bifidobacteria by
evaluating the role of Toll-like receptor (TLR)-2 and TLR negative regulators
in the regulation of proinflammatory cytokines production and MAPK, NF-κB
and PI3K pathways activation in BIE cells. Five bifidobacteria strains were
evaluated in this study and according to their
capacity to modulate the inflammatory response of BIE cells. Despite the
unique effect of each strain, four common points were found when comparing the
effect of the high and moderate anti-inflammatory strains: 1) Upregulation of
TLR negative regulators and the intensity of that upregulation was related to
the different immunomodulatory capacity of each bifidobacteria strain; 2) The balance between MAPK activation and
MKP-1 upregulation affected the anti-inflammatory effect of bifidobacteria in
BIE cells; 3) The inhibition of PI3K pathway was related
to the anti-inflammatory effect of bifidobacteria; 4) The immunoregulatory effect of bifidobacteria in BIE cells is
partially dependent on TLR2. This study shows that BIE cells can be used for
the selection of immunoregulatory bifidobacteria and for studying the
mechanisms involved in the protective activity of immunobiotics against
TLR4-induced inflammatory damage. In addition, we have demonstrated that the
anti-inflammatory effect of bifidobacteria was achieved by a complex interaction
of multiple TLRs negative regulators as well as the inhibition/activation of
multiple signaling pathways.