Human serum amyloid A3 peptide enhances intestinal MUC3 expression and inhibits EPEC adherence.
We previously determined that the N-terminal region of bovine mammary-associated serum amyloid A3 (M-SAA3) increased intestinal mucin MUC3 levels in HT29 human intestinal cells by approximately 2.5-fold, relative to untreated cells. This study shows that the human M-SAA3 N-terminal peptide further enhances MUC3 transcript levels by approximately 4.3-fold in these cells (p<0.02), implicating a species-specific interaction. Furthermore, immunofluorescence and immunoblot analysis using a MUC3-specific monoclonal antibody confirms that the human M-SAA3 peptide stimulates MUC3 protein expression and secretion by the HT29 cells. More importantly, pretreatment of the cells with the peptide causes a subsequent 73% decrease in the adherence of enteropathogenic Escherichia coli (EPEC) to these cells, relative to untreated cells (p<0.01). The intestinal mucin MUC3 has been shown to provide a protective barrier in the gut and inhibit adherence of pathogens to the gut wall. Therefore, a means to increase MUC3 protein expression by a colostrum-associated peptide or protein may be a highly effective prophylactic treatment for the prevention of gastrointestinal diseases such as necrotizing enterocolitis and infectious diarrhea.
Larson
Marilynn A
MA
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Wei
Shu H
SH
Weber
Annika
A
Mack
David R
DR
McDonald
Thomas L
TL
D000595:Amino Acid Sequence; D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects*; D002417:Cattle; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects / Q000472:pathogenicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology*; D007700:Kinetics; D008856:Microscopy, Fluorescence; D055263:Mucin-3; D009077:Mucins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D000685:Serum Amyloid A Protein / Q000737:chemistry / Q000494:pharmacology*
D055263:Mucin-3; D009077:Mucins; D010455:Peptides; D012333:RNA, Messenger; C489625:SAA3P protein, human; D000685:Serum Amyloid A Protein