Osteopontin/Eta-1 upregulated in Crohn's disease regulates the Th1 immune response

Toshiro Sato, T. Nakai, N. Tamura, S. Okamoto, K. Matsuoka, A. Sakuraba, T. Fukushima, T. Uede, T. Hibi

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Background and aims: The pathogenesis of Crohn's disease (CD), a chronic inflammatory bowel disease characterised by a Th1 immune response, remains unclear. Osteopontin (OPN) is a phosphoprotein known as an adhesive bone matrix protein. Recent studies have shown that OPN plays an important role in lymphocyte migration, granuloma formation, and interleukin 12 (IL-12) production. The present study investigated expression and the pathophysiological role of OPN in CD. Methods: Plasma OPN concentration was measured by enzyme linked immunosorbent assay. Expression of OPN in human intestinal mucosa was determined using reverse transcription-polymerase chain reaction and western blot, and localisation of OPN was examined by immunohistochemistry. Expression of integrin s, an OPN receptor, on lamina propria mononuclear cells (LPMC) was assessed by flow cytometry. Functional activation of OPN in LPMC was investigated by measuring the production of cytokines. Results: Plasma OPN concentration was significantly higher in patients with CD compared with normal controls or patients with ulcerative colitis (UC). OPN was upregulated in intestinal mucosa from UC and CD patients. OPN producing cells were epithelial or IgG producing plasma cells, or partial macrophages. OPN was detected in areas surrounding granuloma from mucosa in CD. Integrin βs expressing macrophages infiltrated inflamed mucosa in UC and CD; in contrast, there was no expression of integrin βs on intestinal macrophages in normal mucosa. OPN induced production of IL-12 from LPMC in CD but not in normal controls or UC. Conclusions: Increased OPN expression facilitates cytokine production and is closely involved in the Th1 immune response associated with CD.

Original languageEnglish
Pages (from-to)1254-1262
Number of pages9
JournalGut
Volume54
Issue number9
DOIs
Publication statusPublished - 2005 Sep

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Osteopontin
Crohn Disease
Mucous Membrane
Ulcerative Colitis
Integrins
Macrophages
Intestinal Mucosa
Interleukin-12
Granuloma
Cytokines
Bone Matrix
Phosphoproteins
Plasma Cells
Inflammatory Bowel Diseases
Adhesives
Reverse Transcription

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Sato, T., Nakai, T., Tamura, N., Okamoto, S., Matsuoka, K., Sakuraba, A., ... Hibi, T. (2005). Osteopontin/Eta-1 upregulated in Crohn's disease regulates the Th1 immune response. Gut, 54(9), 1254-1262. https://doi.org/10.1136/gut.2004.048298

Osteopontin/Eta-1 upregulated in Crohn's disease regulates the Th1 immune response. / Sato, Toshiro; Nakai, T.; Tamura, N.; Okamoto, S.; Matsuoka, K.; Sakuraba, A.; Fukushima, T.; Uede, T.; Hibi, T.

In: Gut, Vol. 54, No. 9, 09.2005, p. 1254-1262.

Research output: Contribution to journalArticle

Sato, T, Nakai, T, Tamura, N, Okamoto, S, Matsuoka, K, Sakuraba, A, Fukushima, T, Uede, T & Hibi, T 2005, 'Osteopontin/Eta-1 upregulated in Crohn's disease regulates the Th1 immune response', Gut, vol. 54, no. 9, pp. 1254-1262. https://doi.org/10.1136/gut.2004.048298
Sato T, Nakai T, Tamura N, Okamoto S, Matsuoka K, Sakuraba A et al. Osteopontin/Eta-1 upregulated in Crohn's disease regulates the Th1 immune response. Gut. 2005 Sep;54(9):1254-1262. https://doi.org/10.1136/gut.2004.048298
Sato, Toshiro ; Nakai, T. ; Tamura, N. ; Okamoto, S. ; Matsuoka, K. ; Sakuraba, A. ; Fukushima, T. ; Uede, T. ; Hibi, T. / Osteopontin/Eta-1 upregulated in Crohn's disease regulates the Th1 immune response. In: Gut. 2005 ; Vol. 54, No. 9. pp. 1254-1262.
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