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Chemotactic and Immunoregulatory Properties of Bone Cells are Modulated by Endotoxin-Stimulated Lymphocytes

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Abstract

In our study, we explored the bidirectional communication via soluble factors between bone cells and endotoxin-stimulated splenic lymphocytes in an in vitro coculture model that mimics the inflammatory environment. Both the ability of lymphocytes to affect differentiation and immune properties of bone cells, osteoblasts (OBL) and osteoclasts (OCL), and of bone cells to modulate cytokine and activation profile of endotoxin-stimulated lymphocytes were tested. LPS-pulsed lymphocytes enhanced OCL but inhibited OBL differentiation and increased the RANKL/OPG ratio, and, at the same time, upregulated chemotactic properties of bone cells, specifically CCL2, CCL5, and CXCL10 in OCL and CCL5 and CXCL13 in OBL. In parallel, bone cells had immunosuppressive effects by downregulating the lymphocyte expression of interleukin (IL)-1, IL-6, TNF-α and co-stimulatory molecules. OCL stimulated the production of osteoclastogenic cytokine RANKL in T lymphocytes. The anti-inflammatory effect, especially of OBL, suggests a possible compensatory mechanism to limit the inflammatory reaction during infection.

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Acknowledgments

Special thanks to Department of Immunology, Clinical Institute of Laboratory Diagnosis, University Clinical Hospital Centre Zagreb, Croatia. We thank Ms. K Zrinski-Petrović for her technical assistance. This work was supported by Croatian Ministry of Science, Education and Sports research grants (grant numbers 108–1080229–0140, 108–1080229–0142, 108–1080229–0341).

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Authors and Affiliations

  1. Department of Physiology and Immunology, University of Zagreb School of Medicine, Salata 3, 10000, Zagreb, Croatia

    Hrvoje Cvija, Sanja Ivcevic & Danka Grcevic

  2. Department of Anatomy, University of Zagreb School of Medicine, Zagreb, Croatia

    Natasa Kovacic & Vedran Katavic

  3. Department of Immunology, University of Connecticut Health Center, Farmington, CT, USA

    Hector Leonardo Aguila

  4. Department of Research in Biomedicine and Health, University of Split School of Medicine, Split, Croatia

    Ana Marusic

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  1. Hrvoje Cvija
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  2. Natasa Kovacic
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Correspondence to Danka Grcevic.

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Cvija, H., Kovacic, N., Katavic, V. et al. Chemotactic and Immunoregulatory Properties of Bone Cells are Modulated by Endotoxin-Stimulated Lymphocytes. Inflammation 35, 1618–1631 (2012). https://doi.org/10.1007/s10753-012-9477-y

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