Abstract
Commensal bacteria and their products provide beneficial effects to the mammalian gut by stimulating epithelial cell turnover and enhancing wound healing, without activating overt inflammation. We hypothesized that N-formylpeptide receptors, which bind bacterial N-formylpeptides and are expressed by intestinal epithelial cells, may contribute to these processes. Here we report that formylpeptide receptor-2 (FPR2), which we show is expressed on the apical and lateral membranes of colonic crypt epithelial cells, mediates N-formylpeptide- dependent epithelial cell proliferation and renewal. Colonic epithelial cells in FPR2-deficient mice displayed defects in commensal bacterium-dependent homeostasis as shown by the absence of responses to N-formylpeptide stimulation, shortened colonic crypts, reduced acute inflammatory responses to dextran sulfate sodium (DSS) challenge, delayed mucosal restoration after injury, and increased azoxymethane-induced tumorigenesis. These results indicate that FPR2 is critical in mediating homeostasis, inflammation, and epithelial repair processes in the colon.
| Original language | English |
|---|---|
| Pages (from-to) | 1694-1704 |
| Number of pages | 11 |
| Journal | Journal of Clinical Investigation |
| Volume | 123 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 1 2013 |
| Externally published | Yes |
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- Medicine(all)
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Formylpeptide receptor-2 contributes to colonic epithelial homeostasis, inflammation, and tumorigenesis. / Chen, Keqiang; Liu, Mingyong; Liu, Ying; Yoshimura, Teizo; Shen, Wei; Le, Yingying; Durum, Scott; Gong, Wanghua; Wang, Chunyan; Gao, Ji Liang; Murphy, Philip M.; Wang, Ji Ming.
In: Journal of Clinical Investigation, Vol. 123, No. 4, 01.04.2013, p. 1694-1704.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Formylpeptide receptor-2 contributes to colonic epithelial homeostasis, inflammation, and tumorigenesis
AU - Chen, Keqiang
AU - Liu, Mingyong
AU - Liu, Ying
AU - Yoshimura, Teizo
AU - Shen, Wei
AU - Le, Yingying
AU - Durum, Scott
AU - Gong, Wanghua
AU - Wang, Chunyan
AU - Gao, Ji Liang
AU - Murphy, Philip M.
AU - Wang, Ji Ming
PY - 2013/4/1
Y1 - 2013/4/1
N2 - Commensal bacteria and their products provide beneficial effects to the mammalian gut by stimulating epithelial cell turnover and enhancing wound healing, without activating overt inflammation. We hypothesized that N-formylpeptide receptors, which bind bacterial N-formylpeptides and are expressed by intestinal epithelial cells, may contribute to these processes. Here we report that formylpeptide receptor-2 (FPR2), which we show is expressed on the apical and lateral membranes of colonic crypt epithelial cells, mediates N-formylpeptide- dependent epithelial cell proliferation and renewal. Colonic epithelial cells in FPR2-deficient mice displayed defects in commensal bacterium-dependent homeostasis as shown by the absence of responses to N-formylpeptide stimulation, shortened colonic crypts, reduced acute inflammatory responses to dextran sulfate sodium (DSS) challenge, delayed mucosal restoration after injury, and increased azoxymethane-induced tumorigenesis. These results indicate that FPR2 is critical in mediating homeostasis, inflammation, and epithelial repair processes in the colon.
AB - Commensal bacteria and their products provide beneficial effects to the mammalian gut by stimulating epithelial cell turnover and enhancing wound healing, without activating overt inflammation. We hypothesized that N-formylpeptide receptors, which bind bacterial N-formylpeptides and are expressed by intestinal epithelial cells, may contribute to these processes. Here we report that formylpeptide receptor-2 (FPR2), which we show is expressed on the apical and lateral membranes of colonic crypt epithelial cells, mediates N-formylpeptide- dependent epithelial cell proliferation and renewal. Colonic epithelial cells in FPR2-deficient mice displayed defects in commensal bacterium-dependent homeostasis as shown by the absence of responses to N-formylpeptide stimulation, shortened colonic crypts, reduced acute inflammatory responses to dextran sulfate sodium (DSS) challenge, delayed mucosal restoration after injury, and increased azoxymethane-induced tumorigenesis. These results indicate that FPR2 is critical in mediating homeostasis, inflammation, and epithelial repair processes in the colon.
UR - http://www.scopus.com/inward/record.url?scp=84875842540&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875842540&partnerID=8YFLogxK
U2 - 10.1172/JCI65569
DO - 10.1172/JCI65569
M3 - Article
C2 - 23454745
AN - SCOPUS:84875842540
VL - 123
SP - 1694
EP - 1704
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 4
ER -