title: Formylpeptide receptor-2 contributes to colonic epithelial homeostasis, inflammation, and tumorigenesis.
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.
authors: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA.
authors: Keqiang
authors: K
authors: Chen
authors: Mingyong
authors: M
authors: Liu
authors: Ying
authors: Y
authors: Liu
authors: Teizo
authors: T
authors: Yoshimura
authors: Wei
authors: W
authors: Shen
authors: Yingying
authors: Y
authors: Le
authors: Scott
authors: S
authors: Durum
authors: Wanghua
authors: W
authors: Gong
authors: Chunyan
authors: C
authors: Wang
authors: Ji-Liang
authors: JL
authors: Gao
authors: Philip M
authors: PM
authors: Murphy
authors: Ji Ming
authors: JM
authors: Wang
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000382:microbiology; D003106:Colon / Q000473:pathology*; D003110:Colonic Neoplasms / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D016264:Dextran Sulfate; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D015870:Gene Expression; D006706:Homeostasis; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D044042:Receptors, Formyl Peptide / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D016207:Cytokines; C469988:Fpr1 protein, mouse; D018836:Inflammation Mediators; D019394:Ki-67 Antigen; D044042:Receptors, Formyl Peptide; C481578:formyl peptide receptor 2, mouse; D016264:Dextran Sulfate