Expression of the antimicrobial peptide alpha-defensin/cryptdins in intestinal crypts decreases at the initial phase of intestinal inflammation in a model of inflammatory bowel disease, IL-10-deficient mice.
BACKGROUND
The etiology of inflammatory bowel disease (IBD) is associated with an altered microflora due to a failure of the immune system. This study investigated the expression of the intestinal antimicrobial peptide alpha-defensin, which plays a pivotal role in the regulation of the intestinal microflora in a representative model of IBD, interleukin (IL)-10-deficient mice.


METHODS
The expression of alpha-defensin/cryptdins in IL-10-deficient mice was assessed by real-time polymerase chain reaction (PCR) and acid/urea polyacrylamide gel (AU-PAGE). The alteration of alpha-defensin/cryptdins expression was compared with the inflammatory grade of mice intestine at various weeks from birth.


RESULTS
The weight, length, and inflammation grade of the mouse intestines were assessed at 5, 7, 9, 11, 13, and 15 weeks from birth. While the weight of the large intestine was heavier at 15 weeks after birth in the IL-10-deficient mice than in the control mice, histological inflammation began from 7 weeks after birth. Real-time PCR and AU-PAGE identified a significant decrease in the expression of alpha-defensin/cryptdins at 7 weeks after birth in the IL-10 knockout mice, thus illustrating the involvement of alpha-defensin/cryptdins in the etiology of the intestinal inflammation in IBD. This study also identified the expression of alpha-defensin/cryptdins to be inversely proportional to age until 11 weeks, suggesting a relationship between the formation of the intestinal microflora and a reduction in the expression of alpha-defensin/cryptdins.


CONCLUSIONS
The altered expression of antimicrobial peptide alpha-defensin may cause the onset of intestinal inflammation due to a failure to regulate intestinal microflora.
Inaba
Yuhei
Y
Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical College, Asahikawa, Japan.
Ashida
Toshifumi
T
Ito
Takahiro
T
Ishikawa
Chisato
C
Tanabe
Hiroki
H
Maemoto
Atsuo
A
Watari
Jiro
J
Ayabe
Tokiyoshi
T
Mizukami
Yusuke
Y
Fujiya
Mikihiro
M
Kohgo
Yutaka
Y
D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism; D015153:Blotting, Western; D004195:Disease Models, Animal; D007249:Inflammation / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D016753:Interleukin-10 / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011498:Protein Precursors / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023084:alpha-Defensins / Q000378:metabolism*
D000890:Anti-Infective Agents; D011498:Protein Precursors; D012333:RNA, Messenger; D023084:alpha-Defensins; C059569:cryptdin; D016753:Interleukin-10