Reduced expression of basal and probiotic-inducible G-CSF in intestinal mononuclear cells is associated with inflammatory bowel disease
Article first published online: 4 DEC 2008
Copyright © 2008 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 15, Issue 4, pages 515–525, April 2009
How to Cite
Martins, A. J., Colquhoun, P., Reid, G. and Kim, S. O. (2009), Reduced expression of basal and probiotic-inducible G-CSF in intestinal mononuclear cells is associated with inflammatory bowel disease. Inflamm Bowel Dis, 15: 515–525. doi: 10.1002/ibd.20808
- Issue published online: 16 MAR 2009
- Article first published online: 4 DEC 2008
- Manuscript Accepted: 29 SEP 2008
- Manuscript Received: 3 SEP 2008
- National Sciences and Research Council of Canada (NSERC)
- Crohn's and Colitis Foundation of Canada
Background: Granulocyte-colony stimulating factor (G-CSF) is a pleiotropic cytokine involved in the hematopoiesis of granulocytes, neuroprotection, and immunomodulation. Previously, we have shown that probiotic Lactobacillus rhamnosus GR-1 induces G-CSF production from bone marrow-derived macrophages. Whether this probiotic also induces G-CSF in intestinal mononuclear cells is unknown.
Methods: G-CSF release in response to L. rhamnosus GR-1 was analyzed in isolated intestinal lamina propria mononuclear cells from inflammatory bowel disease (IBD) and non-IBD patients. The effects of G-CSF on proinflammatory cytokine production in human peripheral blood mononuclear cells and intestinal tissue from C57BL/6 wildtype and G-CSF receptor knockout mice was examined.
Results: Normal mouse or human intestinal lamina propria cells constitutively express high levels of G-CSF, of which production was further enhanced by exogenous L. rhamnosus GR-1. However, cells obtained from IBD patients showed reduced G-CSF production under basal conditions and also lower production after exogenous GR-1 treatments. Intestinal tissue samples isolated from G-CSF receptor-deficient mice constitutively expressed higher levels of TNFα, IL-23, and IL-12 than those from wildtype mice, and pretreatment of G-CSF suppressed lipopolysaccharide (LPS)-induced IL-23 in human peripheral blood mononuclear cells.
Conclusions: These results suggest that high G-CSF production induced by commensals such as L. rhamnosus is important in maintaining normal immunological homeostasis in the intestine and defects in the production of G-CSF are associated with IBD.
(Inflamm Bowel Dis 2008)