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Increased IL-10 production during spontaneous apoptosis of monocytes
Malgorzata Bzowska1, Krzysztof Guzik, Katarzyna Barczyk
1Department of Immunology, Institute of Molecular Biology, Jagiellonian University, Cracow, Poland.
Insights
Apoptotic cells alter monocyte cytokine profiles, increasing interleukin-10 (IL-10) and decreasing pro-inflammatory cytokines. This interaction influences T-cell responses, suggesting a role in immune regulation during inflammation resolution.
Area of Science:
- Immunology
- Cell Biology
Background:
- Monocytes/macrophages interact with apoptotic cells in vitro and in vivo.
- Apoptosis influences immune cell function and cytokine production.
Purpose of the Study:
- To investigate how monocyte apoptosis affects cytokine production.
- To explore the immunoregulatory role of apoptotic cells in immune responses.
Main Methods:
- In vitro culture of monocytes and neutrophils.
- Flow cytometry for cell staining (Annexin V, intracellular cytokines).
- Analysis of cytokine production (IL-10, TNF-alpha, IL-1beta, IFN-gamma) at protein and mRNA levels.
Main Results:
- Spontaneous monocyte apoptosis up-regulated lipopolysaccharide (LPS)-induced interleukin-10 (IL-10) production while reducing pro-inflammatory cytokines.
- Increased IL-10 production by non-apoptotic monocytes resulted from interactions with apoptotic cells.
- Apoptotic monocytes reduced IFN-gamma production by CD4+ T cells, partially reversible by anti-IL-10 antibodies.
Conclusions:
- Apoptotic cells modulate monocyte cytokine profiles, promoting an anti-inflammatory environment.
- Interactions between apoptotic and non-apoptotic cells are crucial for immune regulation.
- These findings highlight mechanisms involved in inflammation resolution and immune response modulation.
Abstract:
Monocytes/macrophages undergo apoptosis and are in contact with apoptotic cells both in vitro and in vivo. The data show that monocytes undergoing spontaneous apoptosis in vitro change their cytokine production profile. We demonstrate that the lipopolysaccharide (LPS)-induced production of interleukin-10 (IL-10) is up-regulated, while production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) is either not affected or reduced. These differences seen both at the protein and mRNA level directly correlate with the appearance of apoptotic cells in the culture. Flow cytometry analysis using double staining, surface with annexin V and intracellular with anti-IL-10, suggested that annexin V-negative monocytes are the predominant source of IL-10. Analysis of sorted populations of monocytes indicated that the increase in IL-10 synthesis appears to result from direct interactions between non-apoptotic and apoptotic cells at the time of stimulation. Also non-apoptotic, freshly isolated monocytes produced more IL-10 upon stimulation with LPS, Staphylococcus aureus or zymosan when apoptotic neutrophils were added to the culture. In contrast, monocyte-derived macrophages did not produce more IL-10 in the presence of apoptotic neutrophils. Finally, we found that the presence of apoptotic monocytes in the culture may influence specific immune responses. The data show that in the presence of annexin V-positive monocytes CD4-positive memory T cells produce less IFN-gamma upon stimulation with purified protein derivative of tuberculin, which could be partially reversed by anti-IL-10 neutralizing antibodies. We conclude that these findings might illustrate the mechanisms operating within an inflammatory site and play an important immunoregulatory role during the resolution of inflammation and specific immune responses.