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Inflammation reduces the response to forskolin and expression of the NaHCO 3 cotransporter, NBCe1, in the proximal colon of IL10 −/− mice
Author(s) -
Fan Shujun,
Schultz Michael,
Butt Grant
Publication year - 2013
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.27.1_supplement.949.6
Subject(s) - inflammation , endocrinology , medicine , cotransporter , ussing chamber , bumetanide , forskolin , chemistry , secretion , biology , stimulation , organic chemistry , sodium
The cause of the reduced anion secretion in the inflamed intestine is unknown. In this study, the effect of proximal colonic (PC) inflammation on electrogenic anion secretion and expression of associated transport proteins were investigated. Interleukin10‐knockout (IL10 −/− ) mice infected with Helicobacter typhlonius were used as a model of inflammation and uninfected, asymptomatic IL10 −/− mice served as controls. Electrogenic anion secretion was measured in the Ussing chamber and protein expression determined with immunohistochemistry and Western blotting. The short circuit current (I sc ) response to forskolin was reduced in the inflamed PC (ΔI sc con=99.4±13.5μAcm −2 ; ΔI sc inflamed=60.3±10.9μAcm −2 , X±SEM, n=8, P<0.05). This was due to a decrease in the 4,4′‐diisothiocyanatostilbene‐2,2′‐disulfonic acid‐sensitive (500 μM serosal [s]) component of the response, with no change in the bumetanide‐sensitive (100 μM s) component. Consistent with this, NKCC1 expression was not altered by inflammation, whereas NBCe1 expression was markedly (P<0.001, n=6) reduced, particularly in cells in the upper half of the crypts. This suggests inflammation reduces colonic HCO 3 − secretion, which may affect luminal pH regulation and growth of luminal bacteria, as well as modifying mucus hydration. The resultant dysbiosis and altered intestinal barrier is likely to exacerbate the inflammation. Supported by the OMRF.