IL-12p40 Monomer: A Potential Player in Macrophage Regulation
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-function...
Main Authors: | , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2024-02-01
|
Series: | Immuno |
Subjects: | |
Online Access: | https://www.mdpi.com/2673-5601/4/1/5 |
_version_ | 1797240592805134336 |
---|---|
author | Brian Jeong Kalipada Pahan |
author_facet | Brian Jeong Kalipada Pahan |
author_sort | Brian Jeong |
collection | DOAJ |
description | 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<sup>+</sup>IL-10<sup>+</sup> 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. |
first_indexed | 2024-04-24T18:09:53Z |
format | Article |
id | doaj.art-0cfb7f8fffa74789a46ef86e75d2af8a |
institution | Directory Open Access Journal |
issn | 2673-5601 |
language | English |
last_indexed | 2024-04-24T18:09:53Z |
publishDate | 2024-02-01 |
publisher | MDPI AG |
record_format | Article |
series | Immuno |
spelling | doaj.art-0cfb7f8fffa74789a46ef86e75d2af8a2024-03-27T13:46:47ZengMDPI AGImmuno2673-56012024-02-0141779010.3390/immuno4010005IL-12p40 Monomer: A Potential Player in Macrophage RegulationBrian Jeong0Kalipada Pahan1Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USADepartment of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USAMacrophages 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<sup>+</sup>IL-10<sup>+</sup> 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.https://www.mdpi.com/2673-5601/4/1/5macrophageIL-12p40 monomerIL-10TNFαimmunomodulation |
spellingShingle | Brian Jeong Kalipada Pahan IL-12p40 Monomer: A Potential Player in Macrophage Regulation Immuno macrophage IL-12p40 monomer IL-10 TNFα immunomodulation |
title | IL-12p40 Monomer: A Potential Player in Macrophage Regulation |
title_full | IL-12p40 Monomer: A Potential Player in Macrophage Regulation |
title_fullStr | IL-12p40 Monomer: A Potential Player in Macrophage Regulation |
title_full_unstemmed | IL-12p40 Monomer: A Potential Player in Macrophage Regulation |
title_short | IL-12p40 Monomer: A Potential Player in Macrophage Regulation |
title_sort | il 12p40 monomer a potential player in macrophage regulation |
topic | macrophage IL-12p40 monomer IL-10 TNFα immunomodulation |
url | https://www.mdpi.com/2673-5601/4/1/5 |
work_keys_str_mv | AT brianjeong il12p40monomerapotentialplayerinmacrophageregulation AT kalipadapahan il12p40monomerapotentialplayerinmacrophageregulation |