Abstract
Although osteopontin (OPN) is up-regulated in inflammatory bowel diseases, its role in disease pathogenesis remains controversial. The objective of this study was to determine the role of OPN in host responses to a non-invasive bacterial pathogen, Citrobacter rodentium, which serves as a murine infectious model of colitis. OPN gene knockout and wild-type mice were infected orogastrically with either C. rodentium or Luria-Bertani (LB) broth. Mouse-derived OPN+/+ and OPN-/- fibroblasts were incubated with C. rodentium and attachingeffacing lesions were demonstrated using transmission electron microscopy and immunofluorescence. Colonic expression of OPN was increased by C. rodentium infection of wild-type mice. Furthermore, colonic epithelial cell hyperplasia, the hallmark of C. rodentium infection, was reduced in OPN-/- mice, and spleen enlargement by infection was absent in OPN-/- mice. Rectal administration of OPN to OPN -/- mice restored these effects. There was an 8- to 17-fold reduction in bacterial colonization in OPN-/- mice, compared with wild-type mice, which was accompanied by reduced attaching - effacing lesions, both in infected OPN-/- mice and OPN-/- mouse fibroblasts. Moreover, adhesion pedestals were restored in OPN-/- cells complemented with human OPN. Therefore, lack of OPN results in decreased pedestal formation, colonization, and colonic epithelial cell hyperplasia responses to C. rodentium infection, indicating that OPN impacts disease pathogenesis through bacterial attachment and altered host immune responses.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1320-1332 |
| Number of pages | 13 |
| Journal | American Journal of Pathology |
| Volume | 177 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 2010 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Pathology and Forensic Medicine
Cite this
Osteopontin mediates Citrobacter rodentium-induced colonic epithelial cell hyperplasia and attaching-effacing lesions. / Wine, Eytan; Shen-Tu, Grace; Gareau, Melanie; Goldberg, Harvey A.; Licht, Christoph; Ngan, Bo Yee; Sorensen, Esben S.; Greenaway, James; Sodek, Jaro; Zohar, Ron; Sherman, Philip M.
In: American Journal of Pathology, Vol. 177, No. 3, 09.2010, p. 1320-1332.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Osteopontin mediates Citrobacter rodentium-induced colonic epithelial cell hyperplasia and attaching-effacing lesions
AU - Wine, Eytan
AU - Shen-Tu, Grace
AU - Gareau, Melanie
AU - Goldberg, Harvey A.
AU - Licht, Christoph
AU - Ngan, Bo Yee
AU - Sorensen, Esben S.
AU - Greenaway, James
AU - Sodek, Jaro
AU - Zohar, Ron
AU - Sherman, Philip M.
PY - 2010/9
Y1 - 2010/9
N2 - Although osteopontin (OPN) is up-regulated in inflammatory bowel diseases, its role in disease pathogenesis remains controversial. The objective of this study was to determine the role of OPN in host responses to a non-invasive bacterial pathogen, Citrobacter rodentium, which serves as a murine infectious model of colitis. OPN gene knockout and wild-type mice were infected orogastrically with either C. rodentium or Luria-Bertani (LB) broth. Mouse-derived OPN+/+ and OPN-/- fibroblasts were incubated with C. rodentium and attachingeffacing lesions were demonstrated using transmission electron microscopy and immunofluorescence. Colonic expression of OPN was increased by C. rodentium infection of wild-type mice. Furthermore, colonic epithelial cell hyperplasia, the hallmark of C. rodentium infection, was reduced in OPN-/- mice, and spleen enlargement by infection was absent in OPN-/- mice. Rectal administration of OPN to OPN -/- mice restored these effects. There was an 8- to 17-fold reduction in bacterial colonization in OPN-/- mice, compared with wild-type mice, which was accompanied by reduced attaching - effacing lesions, both in infected OPN-/- mice and OPN-/- mouse fibroblasts. Moreover, adhesion pedestals were restored in OPN-/- cells complemented with human OPN. Therefore, lack of OPN results in decreased pedestal formation, colonization, and colonic epithelial cell hyperplasia responses to C. rodentium infection, indicating that OPN impacts disease pathogenesis through bacterial attachment and altered host immune responses.
AB - Although osteopontin (OPN) is up-regulated in inflammatory bowel diseases, its role in disease pathogenesis remains controversial. The objective of this study was to determine the role of OPN in host responses to a non-invasive bacterial pathogen, Citrobacter rodentium, which serves as a murine infectious model of colitis. OPN gene knockout and wild-type mice were infected orogastrically with either C. rodentium or Luria-Bertani (LB) broth. Mouse-derived OPN+/+ and OPN-/- fibroblasts were incubated with C. rodentium and attachingeffacing lesions were demonstrated using transmission electron microscopy and immunofluorescence. Colonic expression of OPN was increased by C. rodentium infection of wild-type mice. Furthermore, colonic epithelial cell hyperplasia, the hallmark of C. rodentium infection, was reduced in OPN-/- mice, and spleen enlargement by infection was absent in OPN-/- mice. Rectal administration of OPN to OPN -/- mice restored these effects. There was an 8- to 17-fold reduction in bacterial colonization in OPN-/- mice, compared with wild-type mice, which was accompanied by reduced attaching - effacing lesions, both in infected OPN-/- mice and OPN-/- mouse fibroblasts. Moreover, adhesion pedestals were restored in OPN-/- cells complemented with human OPN. Therefore, lack of OPN results in decreased pedestal formation, colonization, and colonic epithelial cell hyperplasia responses to C. rodentium infection, indicating that OPN impacts disease pathogenesis through bacterial attachment and altered host immune responses.
UR - http://www.scopus.com/inward/record.url?scp=77956505984&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77956505984&partnerID=8YFLogxK
U2 - 10.2353/ajpath.2010.091068
DO - 10.2353/ajpath.2010.091068
M3 - Article
C2 - 20651246
AN - SCOPUS:77956505984
VL - 177
SP - 1320
EP - 1332
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 3
ER -