Abstract
Interleukin 11 (IL-11) is a multifunctional cytokine isolated from bone marrow (BM)-derived stromal cells that promotes hematopoiesis and prolongs the life span of lethally irradiated animals. However, the underlying mechanism for the protective effect of IL-11 on BM is unclear. In this study, we explored the effect of IL-11 on irradiated BM cells. Freshly harvested BM cells were pretreated with 20 ng/ml of recombinant IL-11 for 30 min, irradiated with a dose of 0.5 Gy, cultured for 24 h, and then subjected to several assays. In vitro data showed that, as compared to the vehicle controls, IL-11: (1) reduced the production of reactive oxygen species; (2) reduced the alteration of mitochondrial membrane potential; (3) increased MitoTracker staining, suggesting that the number of mitochondria and their functions were better maintained; and (4) reduced apoptosis of BM cells and enhanced BM cell proliferation. In vivo studies of mice pretreated with saline or 100 μg/kg of IL-11 at 12 and 2 h before 10-Gy total body irradiation (TBI) demonstrated that G-CSF and IL-6 were significantly upregulated, whereas IL-2 and IL-4 were reduced. We found that IL-11 protects mitochondrial functions, acts with G-CSF and IL-6 to stimulate the growth of radiation-damaged BM, and reduces the immune response to radiation injury.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Klaunig JE, Wang Z, Pu X, Zhou S (2011) Oxidative stress and oxidative damage in chemical carcinogenesis. Toxicol Appl Pharmacol 254(2):86–99
Paul SR, Bennett F, Calvetti JA et al (1990) Molecular cloning of a cDNA encoding interleukin 11, a stromal cell-derived lymphopoietic and hematopoietic cytokine. Proc Natl Acad Sci USA 87(19):7512–7516
Yin TG, Schendel P, Yang YC (1992) Enhancement of in vitro and in vivo antigen-specific antibody responses by interleukin 11. J Exp Med 175(1):211–216
Du XX, Neben T, Goldman S, Williams DA (1993) Effects of recombinant human interleukin-11 on hematopoietic reconstitution in transplant mice: acceleration of recovery of peripheral blood neutrophils and platelets. Blood 81(1):27–34
Mace K. Bone marrow chimera protocol. Updated September 2007. Available from http://personalpages.manchester.ac.uk/staff/kimberly.mace/pdfs/MaceBMChimera.pdf. Accessed 4 Sept 2012
Leach JK, Van Tuyle G, Lin PS, Schmidt-Ullrich R, Mikkelsen RB (2001) Ionizing radiation-induced, mitochondria-dependent generation of reactive oxygen/nitrogen. Cancer Res 61:3894–3901
MitoTracker® Mitochondrion-selective probes. Updated 25 June 2008. Available from http://tools.invitrogen.com/content/sfs/manuals/mp07510.pdf.invitrogen. Accessed 4 Sept 2012
Trosko JE (2009) Review paper: cancer stem cells and cancer nonstem cells: from adult stem cells or from reprogramming of differentiated somatic cells. Vet Pathol 46(2):176–193
Kondo M, Takeshita T, Ishii N et al (1993) Sharing of the interleukin-2 (IL-2) receptor gamma chain between receptors for IL-2 and IL-4. Science 262(5141):1874–1877
Acknowledgments
This project is supported in part by RC1AI0710519, RC2-AI-01075100, RC1-AI0101274 (NIAID/NIH), and Shands Cancer Center startup funds (University of Florida). We thank Dr. Chihray Liu and the medical physics faculty at UF for ensuring dosimetric accuracy in these experiments and Kate Casey-Sawicki for editing this manuscript.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media New York
About this paper
Cite this paper
Huang, L. et al. (2013). Interleukin 11 Protects Bone Marrow Mitochondria from Radiation Damage. In: Van Huffel, S., Naulaers, G., Caicedo, A., Bruley, D.F., Harrison, D.K. (eds) Oxygen Transport to Tissue XXXV. Advances in Experimental Medicine and Biology, vol 789. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7411-1_35
Download citation
DOI: https://doi.org/10.1007/978-1-4614-7411-1_35
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-7256-8
Online ISBN: 978-1-4614-7411-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)