Antisecretory factor suppresses intestinal inflammation and hypersecretion

Johansson, Ewa; Jennische, Eva; Lange, Stefan; Lönnroth, Ivar

doi:10.1136/gut.41.5.642

Cited by 43 publications

(49 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Introductionmentioning

confidence: 99%

“…In rat jejunal loops, AF inhibited the inflammatory response caused by toxin A from Clostridium difficile (4) . Intestinal exposure to bacterial toxins (4) or intake of specific dietary compounds has proved to enhance the antisecretory and anti-inflammatory activity of endogenous AF (9) . Nowadays, diarrhoeal diseases remain a major global health concern, especially in developing countries where the transmission of infectious gastrointestinal pathogens is favoured by poor hygienic conditions.…”

Section: Introductionmentioning

confidence: 99%

“…The AF protein and its derivatives seem to be the most potent inhibitor of intestinal hypersecretion of various aetiologies. Indeed, less than 1 pmol of human recombinant AF was shown to inhibit CT-induced fluid secretion in a rat model (4) . Torres et al (72) suggested that AF is released as a response to the hypersecretion itself, rather than to the causative agents.…”

Section: Antisecretory Factor and Gut Healthmentioning

confidence: 99%

“…It has been established that AF is synthesised in most tissues of mammals and can be found linked to the 26S proteasome or free in the cytoplasm and/or nucleus (3) . AF has been shown to inhibit enterotoxininduced intestinal hypersecretion in both human and animal subjects (4,5) . In a rat intestinal loop model, 1 pmol of purified AF caused a significant reduction of cholera toxin (CT) and Escherichia coli toxin-induced secretion (6) .…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Antisecretory factor as a potential health-promoting molecule in man and animals

2010

View full text Add to dashboard Cite

Antisecretory factor (AF) is a protein secreted in plasma and other tissue fluids in mammals with proven antisecretory and anti-inflammatory activity; its immunohistological distribution suggests a role in the immune system. The expression level and the distribution of AF protein are altered during an immunological response. Exposure to bacterial toxins induces secretion of AF in plasma, probably reflecting a natural defence mechanism to agents causing diarrhoea, thereby contributing to a favourable clinical outcome and disease termination. An increase of AF levels in plasma by dietary means, such as specially processed cereals (SPC), has been demonstrated in human subjects and animals. Administration of SPC to patients affected by inflammatory bowel disease, gastroenteritis and Ménière's disease relieved symptoms and improved quality of life. A recent study showed the positive effect of SPC diet supplementation on prevention of the effects of exposure to low levels of blast overpressure in rats, reducing the extent of intracranial pressure increase and cognitive function impairment. AF-rich egg yolk powder improved health status in children suffering acute and chronic diarrhoea, reducing the frequency and increasing the consistency of stools. This kind of functional food could be used for prophylaxis in populations exposed to a high risk of morbidity and mortality caused by diarrhoea and as a complementary therapy in patients affected by chronic intestinal inflammatory disease to improve well-being. In pig husbandry AF-inducing diets, owing to their antisecretory activity and anti-inflammatory action, are a suitable option as an alternative to antibiotic growth promoters to counteract post-weaning diarrhoea.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Antisecretory Factor and Gut Healthmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Antisecretory factor as a potential health-promoting molecule in man and animals

2010

View full text Add to dashboard Cite

show abstract

“…The protein was cloned from a prostate cell cDNA library and the full-length cDNA was nearly identical to that reported for S5a, a ubiquitin recognition subunit of the 19S proteasome subunit and antisecretory factor, a secreted protein that regulates water secretion by the large bowel (Johansson et al, 1997). We have named our cloned protein angiocidin due to its in vitro antiangiogenic activity (1).…”

Section: Discussionmentioning

confidence: 82%

Endothelial apoptotic activity of angiocidin is dependent on its polyubiquitin binding activity

et al. 2005

View full text Add to dashboard Cite

We recently cloned the full-length cDNA of a tumour-associated protein. The recombinant protein expressed in bacteria and referred to as angiocidin has potent antitumour activity in vivo and in vitro. Angiocidin inhibits tumour growth and angiogenesis by inducing apoptosis in endothelial cells. Based on the sequence similarity of angiocidin to S5a, one of the major polyubiquitin recognition proteins in eukaryotic cells, we postulated that the antiendothelial activity of angiocidin could be due in part to its polyubiquitin binding activity. In support of this hypothesis, we show that angiocidin binds polyubiquitin in vivo with high affinity and colocalises with ubiquitinated proteins on the surface of endothelial cells. Binding is blocked with an antiubiquitin antibody. Angiocidin treatment of endothelial cells transfected with a proteasome fluorescent reporter protein showed a dose-dependent inhibition of proteasome activity and accumulation of polyubiquitinated proteins. Full-length angiocidin bound polyubiquitin while three angiocidin recombinant proteins whose putative polyubiquitin binding sites were mutated either failed to bind polyubiquitin or had significantly diminished binding activity. The in vitro apoptotic activity of these mutants correlated with their polyubiquitin binding activity. These data strongly argue that the apoptotic activity of angiocidin is dependent on its polyubiquitin binding activity.

show abstract

Binding of the VCHSKT peptide to ceramide‐rich and cholesterol‐rich domains of cell membranes in rat pancreatic glands

Lange

Malmberg

Nygren

2012

Surface & Interface Analysis

View full text Add to dashboard Cite

A peptide with antisecretory effect has been defined and was denoted the antisecretory factor (AF-16) with a sequence of 16 amino acids. A shorter sequence, the AF-6 peptide (VCHSKT, Pepceuticals Ltd, Leicester, England), is readily detected by Time of Flight Secondary Ion Mass Spectrometry (TOF-SIMS), using trifluoroacetic acid (TFA) as ionization catalyzer. Analysis of a reference sample revealed a pseudo-molecular ion at m/z 657 and M + Na + at m/z 679. These peaks were also detected in tissue samples of animals exposed to the peptide. The AF-6 peptide was injected intravenously or sprayed into the nostrils of Sprague-Dawley rats, 250-300 g (n = 5). The animals were anesthetized with isoflurane. Pancreas tissue samples were taken after 2 h and were high-pressure frozen in a Lecia EMPACT, sprayed with 0.1% TFA, and analyzed using a TOF-SIMS V instrument (ION-TOF, GmbH, Münster, Germany) equipped with a Bi 3 + -liquid metal ion gun at the University of Gothenburg. The distribution of the AF-6 peptide could be seen in the pancreas of exposed animals and control animals as high-intensity dots that were heterogeneously distributed in regions with a high intensity of phosphatidylcholine head group m/z 184, indicating a localization to the membrane portion of the pancreatic cells. The peptide was colocalized with a dot-like distribution of galactocylceramide c18:0 and cholesterol. Cholesterol and gal-Cer are known lipid components of specialized membrane areas called lipid rafts. The results indicate that the AF-6 peptide binds to cellular receptors present in such regions of rat pancreatic cells.

show abstract

Antisecretory factor suppresses intestinal inflammation and hypersecretion

Cited by 43 publications

References 31 publications

Antisecretory factor as a potential health-promoting molecule in man and animals

Antisecretory factor as a potential health-promoting molecule in man and animals

Endothelial apoptotic activity of angiocidin is dependent on its polyubiquitin binding activity

Binding of the VCHSKT peptide to ceramide‐rich and cholesterol‐rich domains of cell membranes in rat pancreatic glands

Contact Info

Product

Resources

About