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Inflammation Causes Important Changes in Stomach Tight Junction Structure and Function
Author(s) -
Hagen Susan J,
Zhang Songhua,
Seo Ji Hye,
Fox James G.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1156.4
Subject(s) - tight junction , claudin , paracellular transport , inflammation , barrier function , signal transduction , tumor necrosis factor alpha , mapk/erk pathway , p38 mitogen activated protein kinases , microbiology and biotechnology , stomach , biology , chemistry , immunology , permeability (electromagnetism) , biochemistry , membrane
Little is known about the role of inflammation in tight junction regulation during Helicobacter pylori (HP) infection. We thus examined the role of cytokines in gastric barrier function. Methods Cultured gastric chief cells were incubated with IFN‐γ, TNF‐α, and IL1‐β individually or as a cytomix. Transepithelial resistance (TER) and paracellular permeability were determined without or with specific inhibitors to block IL1‐β receptor‐mediated signaling pathways. Western blots and immunostaining were done using specific antibodies. B6/129 mice infected with HP were used to verify the culture results in a mouse cancer model. Results Cytomix significantly reduced TER and increased paracellular permeability by IL1‐β signaling through p38 MAPK but not other IL1‐induced pathways. Cytomix exposure affected the expression of two important tight junction claudins; claudin18 was completely attenuated and claudin7 was highly up‐regulated. This claudin18/claudin7 “switch” also occurred in tissues from HP‐infected mice. Conclusions Inflammation‐induced IL1 signaling through p38 MAPK causes barrier defects in cultured gastric cells. In particular, claudin18, which is barrier‐forming, is attenuated by IL1 signaling. These data suggest that during inflammation, IL1 regulates the composition and function of tight junctions in stomach. This work was supported by NIH DK015681 and by Departmental funding.