GM-CSF: A Role In Immune And Inflammatory Reactions In ... - PubMed

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Abstract

Granulocyte macrophage colony-stimulating factor (GM-CSF) is a cytokine that promotes myeloid cell development and maturation, and dendritic cell differentiation and survival in vitro. Growing evidence supports the notion that GM-CSF has a major role in some inflammatory and autoimmune reactions and in the host's response to pulmonary infection, but few studies have addressed its functions and importance in the GI tract. Recent studies demonstrated that administration of GM-CSF can result in clinical improvement in patients with Crohn's disease. Mice deficient in GM-CSF (GM-CSF(-/-) ) developed more severe intestinal and systemic infection after an enteric infection, and more severe colitis in response to enteric exposure to dextran sodium sulfate. Both the severity of infection and colitis were largely prevented by GM-CSF administration. Such studies indicate that GM-CSF has an important role in the regulation of intestinal immune and inflammatory responses.

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Figure 1

Figure 1. Granulocyte macrophage colony-stimulating factor produced…

Figure 1. Granulocyte macrophage colony-stimulating factor produced in the intestinal mucosa enhances host protection against…

Figure 1. Granulocyte macrophage colony-stimulating factor produced in the intestinal mucosa enhances host protection against an enteric pathogen Citrobacter rodentium is a naturally occurring mouse pathogen that is widely used to model infections with attaching- and effacing lesion-inducing pathogens in humans (e.g., enteropathogenic and enterohemorrhagic Escherichia coli). After enteric infection of mice with this pathogen, GM-CSF is produced in the colon mucosa. (A) GM-CSF enhances DC survival by decreasing DC apoptosis. (B) GM-CSF, directly or indirectly, induces secretion of the chemoattractant cytokine CCL22 by intestinal epithelial cells, which has a major role in the recruitment and localization of CD11c+ DCs to the subepithelial region of surface epithelial cells. DC: Dendritic cell; GM-CSF: Granulocyte macrophage colony-stimulating factor; IEC: Intestinal epithelial cell.
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References

    1. Fleetwood AJ, Cook AD, Hamilton JA. Functions of granulocyte-macrophage colony-stimulating factor. Crit Rev Immunol. 2005;25(5):405–428. Summary of the major role of granulocyte macrophage-colony stimulating factor (GM-CSF) in inflammation and immunity, and as a regulator of granulocyte and macrophage maturation. Effects of GM-CSF administration, blockade or deficiency are discussed. - PubMed
    1. Hamilton JA. Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol. 2008;8(7):533–544. - PubMed
    1. Dranoff G, Crawford AD, Sadelain M, et al. Involvement of granulocyte-macrophage colony-stimulating factor in pulmonary homeostasis. Science. 1994;264(5159):713–716. - PubMed
    1. Stanley E, Lieschke GJ, Grail D, et al. Granulocyte/macrophage colony-stimulating factor-deficient mice show no major perturbation of hematopoiesis but develop a characteristic pulmonary pathology. Proc Natl Acad Sci USA. 1994;91(12):5592–5596. - PMC - PubMed
    1. Paine R, 3rd, Preston AM, Wilcoxen S, et al. Granulocyte-macrophage colony-stimulating factor in the innate immune response to Pneumocystis carinii pneumonia in mice. J Immunol. 2000;164(5):2602–2609. - PubMed
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