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IL-6 and IL-8 production by human bone marrow stromal cells
F Rougier1, E Cornu, V Praloran
1Laboratoire d'Hématologie Expérimentale, Faculté de Médecine, Limoges, France.
Cytokine
|March 26, 1998
Summary
Human bone marrow stromal cells produce key cytokines Interleukin-6 (IL-6) and Interleukin-8 (IL-8). Their production is influenced by various factors, suggesting stromal cells are a major source within the bone marrow.
Area of Science:
- Immunology
- Cell Biology
- Hematology
Background:
- Bone marrow stromal cells (BMSCs) play a crucial role in hematopoiesis and immune regulation.
- Interleukin-6 (IL-6) and Interleukin-8 (IL-8) are critical cytokines involved in inflammatory and immune responses.
- Understanding the production and regulation of these cytokines by BMSCs is essential for comprehending bone marrow microenvironment dynamics.
Purpose of the Study:
- To investigate the production of IL-6 and IL-8 by human bone marrow stromal cells.
- To determine the factors that regulate the synthesis of IL-6 and IL-8 by BMSCs.
- To explore the potential role of BMSCs as a significant source of IL-6 and IL-8 in the bone marrow.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) was employed to quantify IL-6 and IL-8 levels.
- BMSCs were stimulated with various agents including lipopolysaccharide (LPS), phorbol myristate acetate (PMA), and a panel of recombinant cytokines.
- The effect of protein kinase C (PKC) inhibitor staurosporine and varying concentrations of fetal calf serum (FCS) on cytokine production was assessed.
Main Results:
- BMSCs were confirmed to produce both IL-6 and IL-8.
- Cytokine synthesis was dose-dependently enhanced by LPS and PMA.
- PMA-induced production of IL-6 and IL-8 was significantly reduced by staurosporine, indicating a role for PKC signaling.
- Exogenous IL-6 and IL-8 demonstrated autocrine/paracrine effects, stimulating the production of each other.
- Several other cytokines, including TNF-alpha, SCF, GM-CSF, IL-1 alpha, IL-1 beta, and IL-3, stimulated IL-6 and IL-8 production.
- G-CSF enhanced IL-8, while IL-4 inhibited it, and IL-2, IL-4, and bFGF differentially affected IL-6 production depending on FCS presence.
Conclusions:
- Human bone marrow stromal cells are a significant source of IL-6 and IL-8.
- The production of these cytokines is modulated by inflammatory stimuli, signaling pathways (like PKC), and other cytokines.
- BMSCs contribute to the cytokine network within the bone marrow, potentially regulating local immune and hematopoietic processes.