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Published on: May 31, 2018
IL-12p40 Monomer: A Potential Player in Macrophage Regulation
Brian Jeong1, Kalipada Pahan1,2
1Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA.
Abstract:
Macrophages are myeloid phagocytic leukocytes whose functions are to protect against infections, mediate T-cell responses, and maintain tissue homeostasis. IL-12p40 monomer is a cytokine that is largely produced by macrophages, and it has, for the longest time, been considered a largely non-functional cytokine of the IL-12 family. However, new research has emerged that demonstrates that this p40 monomer may play a bigger role in shaping immune environments. To shed light on the specific effects of p40 monomer on macrophages and their surrounding environment, we showed, through cell culture studies, qPCR, ELISA, and immunofluorescence analyses, that the direct administration of recombinant p40 monomer to RAW 264.7 cells and primary lung macrophages stimulated the production of both pro-inflammatory (TNFα) and anti-inflammatory (IL-10) signals. Accordingly, p40 monomer prevented the full pro-inflammatory effects of LPS, and the neutralization of p40 monomer by mAb a3-3a stimulated the pro-inflammatory effects of LPS. Furthermore, we demonstrated that the intranasal administration of p40 monomer upregulated TNFα+IL-10+ macrophages in vivo in the lungs of mice. Collectively, these results indicate an important immunoregulatory function of p40 monomer in the upregulation of both pro- and anti-inflammatory molecules in macrophages.
Insights
The IL-12p40 monomer, once thought non-functional, actively regulates macrophage immune responses. This cytokine stimulates both pro-inflammatory (TNFα) and anti-inflammatory (IL-10) signals, influencing immune environments.
Area of Science:
- Immunology
- Cell Biology
Background:
- Macrophages are crucial immune cells for infection defense and tissue homeostasis.
- The IL-12p40 monomer, a cytokine produced by macrophages, was historically considered non-functional.
- Emerging research suggests the p40 monomer plays a significant role in modulating immune environments.
Purpose of the Study:
- To investigate the specific effects of the IL-12p40 monomer on macrophages and their surrounding environment.
- To elucidate the immunoregulatory functions of the p40 monomer in immune responses.
Main Methods:
- Cell culture studies using RAW 264.7 cells and primary lung macrophages.
- Quantitative PCR (qPCR), ELISA, and immunofluorescence analyses.
- In vivo studies involving intranasal administration of p40 monomer in mice.
Main Results:
- Direct administration of recombinant p40 monomer stimulated both pro-inflammatory (TNFα) and anti-inflammatory (IL-10) cytokine production in macrophages.
- p40 monomer administration inhibited the full pro-inflammatory effects of lipopolysaccharide (LPS).
- Neutralization of p40 monomer enhanced LPS-induced pro-inflammatory responses, and intranasal administration upregulated TNFα+IL-10+ macrophages in vivo.
Conclusions:
- The IL-12p40 monomer possesses significant immunoregulatory functions.
- p40 monomer plays a key role in upregulating both pro- and anti-inflammatory molecules in macrophages.
- This cytokine actively shapes the immune environment by modulating macrophage responses.
