DOI: 10.1084/jem.185.11.1977. Selective Suppression of Interleukin-12 Induction after Macrophage Receptor Ligation

Selective Suppression of Interleukin-12 Induction after Macrophage Receptor Ligation

10.1084/jem.185.11.1977

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

Abstract

Interleukin (IL)-12 is a monocyte- and macrophage-derived cytokine that plays a crucial role in both the innate and the acquired immune response. In this study, we examined the effects that ligating specific macrophage receptors had on the induction of IL-12 by lipopolysaccharide (LPS). We report that ligation of the macrophage Fcγ, complement, or scavenger receptors inhibited the induction of IL-12 by LPS. Both mRNA synthesis and protein secretion were diminished to near-undetectable levels following receptor ligation. Suppression was specific to IL-12 since IL-10 and tumor necrosis factor-α (TNF-α) production were not inhibited by ligating macrophage receptors. The results of several different experimental approaches suggest that IL-12 downregulation was due to extracellular calcium influxes that resulted from receptor ligation. First, preventing extracellular calcium influxes, by performing the assays in EGTA, abrogated FcγR-mediated IL-12(p40) mRNA suppression. Second, exposure of macrophages to the calcium ionophores, ionomycin or A23187, mimicked receptor ligation and inhibited IL-12(p40) mRNA induction by LPS. Finally, bone marrow–derived macrophages from FcR γ chain–deficient mice, which fail to flux calcium after receptor ligation, failed to inhibit IL-12(p40) mRNA induction. These results indicate that the calcium influxes that occur as a result of receptor ligation are responsible for inhibiting the induction of IL-12 by LPS. Hence, the ligation of phagocytic receptors on macrophages can lead to a dramatic decrease in IL-12 induction. This downregulation may be a way of limiting proinflammatory responses of macrophages to extracellular pathogens, or suppressing the development of cell-mediated immunity to intracellular pathogens.

Bibliography

Sutterwala, F. S., Noel, G. J., Clynes, R., & Mosser, D. M. (1997). Selective Suppression of Interleukin-12 Induction after Macrophage Receptor Ligation. The Journal of Experimental Medicine, 185(11), 1977â1985.

Authors 4

Fayyaz S. Sutterwala (first)
Gary J. Noel (additional)
Raphael Clynes (additional)
David M. Mosser (additional)

References 41 Referenced 270

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{'key': '2023072507065456100_B12', 'first-page': '423', 'article-title': 'The role of interleukin12 in acquired immunity to Mycobacterium tuberculosisinfection', 'volume': '84', 'author': 'Cooper', 'year': '1995', 'journal-title': 'Immunology'} / Immunology / The role of interleukin12 in acquired immunity to Mycobacterium tuberculosisinfection by Cooper (1995)
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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:49 p.m.)
Deposited	2 years, 1 month ago (July 25, 2023, 3:40 a.m.)
Indexed	3 days, 2 hours ago (Sept. 3, 2025, 6:59 a.m.)
Issued	28 years, 3 months ago (June 2, 1997)
Published	28 years, 3 months ago (June 2, 1997)
Published Online	28 years, 3 months ago (June 2, 1997)
Published Print	28 years, 3 months ago (June 2, 1997)

Funders 0

None

BibTeX

@article{Sutterwala_1997, title={Selective Suppression of Interleukin-12 Induction after Macrophage Receptor Ligation}, volume={185}, ISSN={1540-9538}, url={http://dx.doi.org/10.1084/jem.185.11.1977}, DOI={10.1084/jem.185.11.1977}, number={11}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Sutterwala, Fayyaz S. and Noel, Gary J. and Clynes, Raphael and Mosser, David M.}, year={1997}, month=jun, pages={1977–1985} }

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