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Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114
LPS elicits several immediate proinflammatoy responses in
peripheral blood leukocytes via a recently described pathway including
CD14, Toll-like receptors (TLR), serine-threonine kinases, and NF-
B
transcription factor. However, the functional responses of intestinal
epithelial cells (IEC) to stimulation with LPS are unknown. Expression
of mRNA and protein for CD14 and TLRs were assessed by RT-PCR,
immunoblotting, and immunohistochemistry in mouse and human IEC lines.
LPS-induced activation of signaling pathways (p42/p44 mitogen-activated
protein kinase (MAPK), c-Jun NH2-terminal kinase (JNK),
p38, p65, NF-B) were assessed by immunoblotting and gel shifts. CD14
mRNA and protein expression were not detectable in IEC. However, human
TLR2, TLR3, and TLR4 mRNA were present in IEC. TLR4 protein was
expressed in all cell lines; however, TLR2 protein was absent in HT29
cells. Immunofluorescent staining of T84 cells demonstrated the
cell-surface presence of the TLRs. LPS-stimulation of IEC resulted in
activation (>1.5-fold) of the three members of the MAPK family. In
contrast, LPS did not significantly induce activation of JNK and p38 in
CMT93 cells, p38 in T84 cells and MAPK and JNK in HT29 cells.
Downstream, LPS activated NF-B in IEC in a time-, dose-, and
serum-dependent manner. IEC express TLRs that appear to mediate LPS
stimulation of specific intracellular signal transduction pathways in
IEC. Thus, IEC may play a frontline role in monitoring lumenal
bacteria.
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