Reduced expression of basal and probiotic-inducible G-CSF in intestinal mononuclear cells is associated with inflammatory bowel disease

Abstract

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. 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. 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 TNFalpha, 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. 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.