title: Reduced expression of basal and probiotic-inducible G-CSF in intestinal mononuclear cells is associated with inflammatory bowel disease.
abstract: 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 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.
  
  
  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.
authors.affiliation: Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Martins
authors.forename: Patrick
authors.initials: P
authors.lastname: Colquhoun
authors.forename: Gregor
authors.initials: G
authors.lastname: Reid
authors.forename: Sung Ouk
authors.initials: SO
authors.lastname: Kim
mesh_terms: D000818:Animals; D004926:Escherichia coli; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D018664:Interleukin-12 / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D052201:Lacticaseibacillus rhamnosus / Q000254:growth & development / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000166:cytology / Q000276:immunology / Q000382:microbiology*; D019936:Probiotics / Q000494:pharmacology*; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053759:Interleukin-23; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D018664:Interleukin-12