Medicine, Dentistry & Health Sciences Collected Works - Research Publications

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http://hdl.handle.net/11343/241

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Start date: 2010 × End date: 2019 × Type: Abstract ×

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Now showing 1 - 5 of 5
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    High fat diets induce colonic epithelial cell stress and inflammation that is reversed by IL-22
    Gulhane, M ; Murray, L ; Lourie, R ; Tong, H ; Kang, A ; Schreiber, V ; Magor, G ; Denman, S ; Begun, J ; Florin, T ; Perkins, A ; Cuiv, OP ; Mcguckin, M ; Hasnain, SZ (WILEY-BLACKWELL, 2016-08)
    Prolonged high fat diets (HFD) induce low-grade chronic intestinal inflammation in mice, and diets high in saturated fat are a risk factor for the development of human inflammatory bowel diseases. We hypothesized that HFD-induced endoplasmic reticulum (ER)/oxidative stress occur in intestinal secretory goblet cells, triggering inflammatory signaling and reducing synthesis/secretion of proteins that form the protective mucus barrier. In cultured intestinal cells non-esterified long-chain saturated fatty acids directly increased oxidative/ER stress leading to protein misfolding. A prolonged HFD elevated the intestinal inflammatory cytokine signature, alongside compromised mucosal barrier integrity with a decrease in goblet cell differentiation and Muc2, a loss in the tight junction protein, claudin-1 and increased serum endotoxin levels. In Winnie mice, that develop spontaneous colitis, HFD-feeding increased ER stress, further compromised the mucosal barrier and increased the severity of colitis. In obese mice IL-22 reduced ER/oxidative stress and improved the integrity of the mucosal barrier, and reversed microbial changes associated with obesity with an increase in Akkermansia muciniphila. Consistent with epidemiological studies, our experiments suggest that HFDs are likely to impair intestinal barrier function, particularly in early life, which partially involves direct effects of free-fatty acids on intestinal cells, and this can be reversed by IL-22 therapy.
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    TLR2 AND TLR7/8 ACTIVATION PREDICT POST PARTUM HBV FLARES
    Visvanathan, K ; Skinner, N ; Locarnini, S ; Bowden, S ; Lewin, S ; Giles, M ; Sasadeusz, J (ELSEVIER SCIENCE BV, 2012-04)
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    CLINICAL OUTCOMES, VIROLOGICAL CHANGES AND FLARES IN WOMEN WITH CHRONIC HEPATITIS B VIRUS INFECTION DURING PREGNANCY AND POST PARTUM
    Giles, M ; Visvanathan, K ; Lewin, S ; Spelman, T ; Locarnini, S ; Bowden, S ; Sasadeusz, J (ELSEVIER SCIENCE BV, 2012-04)
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    Variation in the IL7R gene influences MS risk, response to therapy and immune cell function
    McKay, F ; Hoe, E ; Parnell, G ; Schibeci, S ; Rajasuriar, R ; Lewin, S ; Stewart, G ; Booth, D (SAGE PUBLICATIONS LTD, 2012-05)
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    The mechanism and application of a superagonistic antibody for human IL-21
    Leong, YA ; Cui, Y ; Chen, Z ; Wightman, F ; Chen, Y ; Lewin, S ; Landay, A ; Mackay, C ; Yu, D (ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2014-11)