Granulocyte-macrophage colony-stimulating factor elicits bone marrow-derived cells that promote efficient colonic mucosal healing

Bernasconi, Eric; Favre, Laurent; Maillard, Michel H.; Bachmann, Daniel; Pythoud, Catherine; Bouzourène, Hanifa; Croze, Ed; Velichko, Sharlene; Parkinson, John F.; Michetti, Pierre; Velin, Dominique

doi:10.1002/ibd.21072

Cited by 76 publications

(86 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GM-CSF has been shown to reduce DSS-induced colitis and decrease the levels of pro-inflammatory cytokines (TNF-and IL-1 ) in colonic tissue samples [295,296]. These results were confirmed recently; GM-CSF decreased the DSS-induced colitis and the expression of pro-inflammatory cytokines.…”

Section: Immune Stimulationsupporting

confidence: 53%

“…These results were confirmed recently; GM-CSF decreased the DSS-induced colitis and the expression of pro-inflammatory cytokines. In addition, the duration of ulcer healing was shorter and epithelial regeneration was facilitated in GM-CSF-treated mice [295]. Based on these preclinical results, a potential role for GM-CSF in the therapy of patients with IBD has been raised.…”

Section: Immune Stimulationmentioning

confidence: 99%

See 1 more Smart Citation

Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

Gyires¹,

Tóth²,

Zádori

2014

CPD

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory condition of the gastrointestinal tract. The two main forms of IBD are Crohn's disease and ulcerative colitis. According to the recent concept the disease is caused by a combination of factors, including genetics, immune dysregulation, barrier dysfunction and the change in microbial flora. Environmental factors, such as changes in diet, antibiotic use, smoking or improved domestic hygiene (e.g. eradication of intestinal helminths) probably contribute to the development and increased prevalence of IBD. Dysregulation of mucosal immunity in IBD causes an overproduction of inflammatory cytokines which resulted in uncontrolled intestinal inflammation. Based on extensive research over the last decade, besides the conventional therapy, there are several novel pathways and specific targets, on which focus new therapeutics. New therapeutics aim 1./ to correct genetic susceptibility by stimulating NOD2 expression, TLR3 signaling or inhibition of TLR4 pathway, 2./ to restore the immune dysregulation by inhibition of pro-inflammatory cytokines (TNF-, IL-6, IL-13, IL-17, IL-18, IL-21), Th1 polarisation (IL-2, IL-12, IL-23, IFN-), T-cell activation, leukocyte adhesion, as well as by immunostimulation (GM-CSF, G-CSF) and anti-inflammatory cytokines (IL-10, IL-11, IFN--1a), 3./ to restore mucosal barrier function and stimulate mucosal healing by different growth factors, such as GH, EGF, KGF, TGF-, VEGF, 4./ to restore the normal bacterial flora by antibiotics, probiotics. However, in spite of these numerous potential targets, the true value and clinical significance of most of the new biologics and molecules are not clear yet.

show abstract

Section: Immune Stimulationsupporting

confidence: 53%

Section: Immune Stimulationmentioning

confidence: 99%

Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

Gyires¹,

Tóth²,

Zádori

2014

CPD

View full text Add to dashboard Cite

show abstract

“…Previous studies of chemically induced colitis in rats revealed that depletion or adhesion blockade of neutrophils aggravated the intestinal histopathology, and promotion of bone marrow-derived granulocyte differentiation facilitated the mucosal repair processes. 28,55,56 One report indicates that neutrophil-derived IL-1b is involved in promoting epithelial restitution and mucosal wound healing after ischemic challenge via a cyclooxygenase-2-dependent mechanism. 57 Previous studies showed that adaptive hypoxia protects the intestinal epithelial barrier integrity via transcriptional regulation of hypoxiainducible factor 1.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil priming by hypoxic preconditioning protects against epithelial barrier damage and enteric bacterial translocation in intestinal ischemia/reperfusion

Huang

et al. 2012

Laboratory Investigation

View full text Add to dashboard Cite

Intestinal ischemia/reperfusion (I/R) induces mucosal barrier dysfunction and bacterial translocation (BT). Neutrophilderived oxidative free radicals have been incriminated in the pathogenesis of ischemic injury in various organs, but their role in the bacteria-containing intestinal tract is debatable. Primed neutrophils are characterized by a faster and higher respiratory burst activity associated with more robust bactericidal effects on exposure to a second stimulus. Hypoxic preconditioning (HPC) attenuates ischemic injury in brain, heart, lung and kidney; no reports were found in the gut. Our aim is to investigate whether neutrophil priming by HPC protects against intestinal I/R-induced barrier damage and bacterial influx. Rats were raised in normoxia (NM) or kept in a hypobaric hypoxic chamber (380 Torr) 17 h/day for 3 weeks for HPC, followed by sham operation or intestinal I/R. Gut permeability was determined by using an ex vivo macromolecular flux assay and an in vivo magnetic resonance imaging-based method. Liver and spleen homogenates were plated for bacterial culturing. Rats raised in HPC showed diminished levels of BT, and partially improved mucosal histopathology and epithelial barrier function compared with the NM groups after intestinal I/R. Augmented cytokineinduced neutrophil chemoattractant (CINC)-1 and -3 levels and myeloperoxidase activity correlated with enhanced infiltration of neutrophils in intestines of HPC-I/R compared with NM-I/R rats. HPC alone caused blood neutrophil priming, as shown by elevated production of superoxide and hydrogen peroxide on stimulation, increased membrane translocation of cytosolic p47 phox and p67 phox , as well as augmented bacterial-killing and phagocytotic activities. Neutrophil depletion reversed the mucosal protection by HPC, and aggravated intestinal leakiness and BT following I/R. In conclusion, neutrophil priming by HPC protects against I/R-induced BT via direct antimicrobial activity by oxidative respiratory bursts and through promotion of epithelial barrier integrity for luminal confinement of enteric bacteria.

show abstract

“…These antibodies are directed against GM-CSF which is a cytokine that is necessary for anti-microbial functions of myeloid cells and that have an important role in the regulation of intestinal mucosal damage, in intestinal immunity and inflammatory responses [10][11][12][13][14]. Mice deficient in GM-CSF had defects in mucosal barrier function with more severe intestinal and systemic infection after enteric infection, more severe colitis after enteric exposure to dextran sodium sulphate or developed transmural ileitis following non-steroidal anti-inflammatory drug (NSAID) exposure [10][11][12][13][14]. GM-CSF therapy improved mucosal repair and could have a role in clinical improvement in CD [10][11][12][13]15].…”

mentioning

confidence: 99%

“…Mice deficient in GM-CSF had defects in mucosal barrier function with more severe intestinal and systemic infection after enteric infection, more severe colitis after enteric exposure to dextran sodium sulphate or developed transmural ileitis following non-steroidal anti-inflammatory drug (NSAID) exposure [10][11][12][13][14]. GM-CSF therapy improved mucosal repair and could have a role in clinical improvement in CD [10][11][12][13]15]. Jurickova et al found that anti-GM-CSF Ab were produced by lamina propria mononuclear cells isolated from CD ileal resection specimens and that peripheral blood contains GM-CSF neutralizing capacity [16].…”

mentioning

confidence: 99%

Clinical Utility of Anti- Granulocyte Macrophage-Colony Stimulating Factor Antibodies in Inflammatory Bowel Disease

Paul¹

2017

JGPLD

View full text Add to dashboard Cite

Granulocyte-macrophage colony-stimulating factor elicits bone marrow-derived cells that promote efficient colonic mucosal healing

Abstract: Our study shows that GM-CSF-dependent stimulation of bone marrow-derived cells during DSS-induced colitis accelerates colonic tissue repair. These data provide a putative mechanism for the observed beneficial effects of GM-CSF therapy in Crohn's disease.

Cited by 76 publications

References 48 publications

Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

Neutrophil priming by hypoxic preconditioning protects against epithelial barrier damage and enteric bacterial translocation in intestinal ischemia/reperfusion

Clinical Utility of Anti- Granulocyte Macrophage-Colony Stimulating Factor Antibodies in Inflammatory Bowel Disease

Contact Info

Product

Resources

About