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M-CSF induces the expression of a membrane-bound form of IL-18 in a subset of human monocytes differentiating in vitro toward macrophages.
- Source :
-
European journal of immunology [Eur J Immunol] 2012 Jun; Vol. 42 (6), pp. 1618-26. - Publication Year :
- 2012
-
Abstract
- IL-18 is a proinflammatory cytokine belonging to the "IL-1 family" that has been shown to play a prominent role in the induction of type 1 immune responses. Here, we show that M-CSF induces the expression of a membrane-bound form of IL-18 (mIL-18) in a subset of human blood monocytes differentiating toward macrophages. While monocytes, DC, and GM-CSF-treated monocytes did not express mIL-18, its expression was detected in approximately 30-40% of M-CSF-primed macrophages differentiating from both CD16(-) and CD16(+) monocytes. Treatment with the caspase-1 inhibitor significantly reduced mIL-18 expression suggesting the requirement of an assembled inflammasome for IL-18 surface expression. Polarization toward M2 did not modify mIL-18 expression. On the contrary, LPS stimulation of both M0 and M2 (mIL-18(+) ) macrophages induced shedding of mIL-18, which was likely mediated by the activation of cellular protease(s). Importantly, the soluble form IL-18 (sIL-18) induced in autologous resting NK cells both the expression of CCR7 and the production of high amounts of IFN-γ, which was virtually abrogated by Ab-mediated neutralization of sIL-18. Overall our data shed new light on the cells and mechanisms leading to the release of sIL-18, the major IFN-γ-inducing factor in both physiological and pathological immune responses.<br /> (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Subjects :
- Caspase 1 physiology
Cells, Cultured
GPI-Linked Proteins analysis
Granulocyte-Macrophage Colony-Stimulating Factor pharmacology
Humans
Interferon-gamma biosynthesis
Interleukin-18 analysis
Macrophages chemistry
Monocytes chemistry
Monocytes cytology
Receptors, IgG analysis
Cell Differentiation
Interleukin-18 physiology
Macrophage Colony-Stimulating Factor pharmacology
Macrophages cytology
Monocytes drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1521-4141
- Volume :
- 42
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- European journal of immunology
- Publication Type :
- Academic Journal
- Accession number :
- 22678914
- Full Text :
- https://doi.org/10.1002/eji.201142173