Intestinal Epithelial Serum Amyloid A Modulates Bacterial Growth In Vitro and Pro-Inflammatory Responses in Mouse Experimental Colitis

<p>Abstract</p> <p>Background</p> <p>Serum Amyloid A (SAA) is a major acute phase protein of unknown function. SAA is mostly expressed in the liver, but also in other tissues including the intestinal epithelium. SAA reportedly has anti-bacterial effects, and because inflammatory bowel diseases (IBD) result from a breakdown in homeostatic interactions between intestinal epithelia and bacteria, we hypothesized that SAA is protective during experimental colitis.</p> <p>Methods</p> <p>Intestinal SAA expression was measured in mouse and human samples. Dextran sodium sulfate (DSS) colitis was induced in SAA 1/2 double knockout (DKO) mice and in wildtype controls. Anti-bacterial effects of SAA1/2 were tested in intestinal epithelial cell lines transduced with adenoviral vectors encoding the CE/J SAA isoform or control vectors prior to exposure to live <it>Escherichia coli</it>.</p> <p>Results</p> <p>Significant levels of SAA1/SAA2 RNA and SAA protein were detected by in situ hybridization and immunohistochemistry in mouse colonic epithelium. SAA3 expression was weaker, but similarly distributed. SAA1/2 RNA was present in the ileum and colon of conventional mice and in the colon of germfree mice. Expression of SAA3 was strongly regulated by bacterial lipopolysaccharides in cultured epithelial cell lines, whereas SAA1/2 expression was constitutive and not LPS inducible. Overexpression of SAA1/2 in cultured epithelial cell lines reduced the viability of co-cultured <it>E. coli</it>. This might partially explain the observed increase in susceptibility of DKO mice to DSS colitis. SAA1/2 expression was increased in colon samples obtained from Crohn's Disease patients compared to controls.</p> <p>Conclusions</p> <p>Intestinal epithelial SAA displays bactericidal properties in vitro and could play a protective role in experimental mouse colitis. Altered expression of SAA in intestinal biopsies from Crohn's Disease patients suggests that SAA is involved in the disease process..</p

Sensing of Dietary Lipids by Enterocytes: A New Role for SR-BI/CLA-1

BACKGROUND: The intestine is responsible for absorbing dietary lipids and delivering them to the organism as triglyceride-rich lipoproteins (TRL). It is important to determine how this process is regulated in enterocytes, the absorptive cells of the intestine, as prolonged postprandial hypertriglyceridemia is a known risk factor for atherosclerosis. During the postprandial period, dietary lipids, mostly triglycerides (TG) hydrolyzed by pancreatic enzymes, are combined with bile products and reach the apical membrane of enterocytes as postprandial micelles (PPM). Our aim was to determine whether these micelles induce, in enterocytes, specific early cell signaling events that could control the processes leading to TRL secretion. METHODOLOGY/PRINCIPAL FINDINGS: The effects of supplying PPM to the apex of Caco-2/TC7 enterocytes were analyzed. Micelles devoid of TG hydrolysis products, like those present in the intestinal lumen in the interprandial period, were used as controls. The apical delivery of PPM specifically induced a number of cellular events that are not induced by interprandial micelles. These early events included the trafficking of apolipoprotein B, a structural component of TRL, from apical towards secretory domains, and the rapid, dose-dependent activation of ERK and p38MAPK. PPM supply induced the scavenger receptor SR-BI/CLA-1 to cluster at the apical brush border membrane and to move from non-raft to raft domains. Competition, inhibition or knockdown of SR-BI/CLA-1 impaired the PPM-dependent apoB trafficking and ERK activation. CONCLUSIONS/SIGNIFICANCE: These results are the first evidence that enterocytes specifically sense postprandial dietary lipid-containing micelles. SR-BI/CLA-1 is involved in this process and could be a target for further study with a view to modifying intestinal TRL secretion early in the control pathway

A late Holocene palaeoenvironmental record from Lake Tizong, northern Cameroon using diatom and carbon stable isotope analyses

A late Holocene record, based on diatom and stable carbon isotopes from Lake Tizong, northern Cameroon, provides a history of environmental changes over the last 4100 years. Several coarser sediment layers among which the two younger ones are of pyroclastic origin interrupt the fine clayey sediment of the core. The detailed chronology of the core supported by 24 radiocarbon C-14 dates and proxies data results revealed an erosive phase registered in the sedimentary column from 2200 to 1500 cal BP. The diatom ecological groups suggest that between 4100 and 2800 cal yrs BP, the lake level was much higher than after corresponding to a relatively greater precipitation minus evaporation (P E) ratio, as well as increased runoff in the lake catchment. These conditions were favourable to the development of C3 plants in the lake catchment as indicated by lower delta C-13 values and higher C/N ratios than after. This hydrological phase is also characterized by eutrophic, turbid and probably circum-neutral to alkaline waters. After this episode, higher delta C-13 values between 2800 and 2500 cal BP suggest increased water use efficiency of terrestrial plants and/or potentially more C4 plant debris input into the lake: an indication of savannas patches developing, due probably to changes in the rainfall distribution. Marked lake-level declines are recorded at 2500, 2200-2100, and at 1400-1000 cal yrs BP. These low-stands are characterized by higher inputs of windblown diatoms (up to 4.2%) than before, which confirms that the NE trade-winds were strengthening. This corresponds primarily to a reduction in the P E ratio, but probably also to greater inter-annual or seasonal variability when drier periods or seasons became more prolonged and intense than previously. Consequently, savannas were maintained as suggested by relatively higher than before delta C-13 values, as well as independently supported by regional pollen data. After 1000 cal BP, the lake-level rose towards sub-modern conditions, with a deep neutral and eutrophic water column. Carbon stable isotopes suggest a reduction of organic matter input, while savannas were maintained despite the return to more humid conditions. The trends of climatic changes observed in the Lake Tizong reveal the variability in timing, magnitude and regional extent of known climatic events

Past environmental and climatic changes during the last 7200 cal yr BP in Adamawa plateau (Northern-Cameroun) based on fossil diatoms and sedimentary carbon isotopic records from Lake Mbalang

Past limnological conditions of Lake Mbalang (7 degrees 19' N, 13 degrees 44' E, altitude: 1130 m) and vegetation type were reconstructed from diatoms and sedimentary stable carbon isotope records (delta C-13) since 7200 cal yr BP. The data showed that before 3600 cal yr BP, the water column was dominantly stable except around 5000-5300 cal yr BP where diatoms evidenced a mixed upper water layer and delta C-13 data suggest more forested vegetation in the landscape. These stable conditions can be explained by a strong monsoon flux and relatively northern position of the ITCZ that entailed high or low rainfall well distributed over the year, allowing the development of mountainous forest taxa. The decreasing trend of the monsoon flux towards the mid-Holocene was affected by several abrupt centennial to millennial-scale weakening at 6700, 5800-6000, 5000-5300, 4500 and 3600 cal yr BP. However, their impact on the vegetation is not visible, probably because rainfall distribution was favourable to forest maintenance or extension. After 3600 cal yr BP, the water column became very mixed as a result of more intense NE trade winds (Harmattan) that led at similar to 3000 cal yr BP to the establishment of savannah in the vegetation landscape. At that time, rainfall was probably reduced following the southward shift of the ITCZ, and the distribution of yearly rainfall was not favourable anymore to forest development. A strong seasonality with a marked dry season was established, conditions that maintained the savannah vegetation until today. Diatom data suggest the lake did not dry up during the last 7200 cal yr BP; however, a low lake level observed at 24002100 cal yr BP is contemporaneous to a climatic event evidenced in several areas of tropical Africa and could correspond to the southernmost position of the ITCZ. Other low lake levels are observed at 1800 and 1400 cal yr BP, after which the lake rose to its present level

Etude de l’absorption intestinale de lipides dans un modèle murin surexprimant au niveau intestinal le Scavenger Receptor Class B type I : SR-BI

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Bridging the translational innovation gap through good biomarker practice

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