期刊
PLOS MEDICINE
卷 3, 期 8, 页码 1310-1319出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pmed.0030277
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资金
- NCI NIH HHS [CA046934, P30 CA046934] Funding Source: Medline
- NHLBI NIH HHS [P01 HL068743, HL-68743] Funding Source: Medline
- NIAID NIH HHS [R56 AI015614, AI-15614, R01 AI015614] Funding Source: Medline
Background Interleukin (IL)-32 is a newly described proinflammatory cytokine that seems likely to play a role in inflammation and host defense. Little is known about the regulation of IL-32 production by primary cells of the immune system. Methods and Findings In the present study, freshly obtained human peripheral blood mononuclear cells were stimulated with different Toll-like receptor (TLR) agonists, and gene expression and synthesis of IL-32 was determined. We demonstrate that the TLR4 agonist lipopolysaccharide induces moderate (4-fold) production of IL-32, whereas agonists of TLR2, TLR3, TLR5, or TLR9, each of which strongly induced tumor necrosis factor a and IL-6, did not stimulate IL-32 production. However, the greatest amount of IL-32 was induced by the mycobacteria Mycobacterium tuberculosis and M. bovis BCG (20-fold over unstimulated cells). IL-32-induced synthesis by either lipopolysaccharide or mycobacteria remains entirely cell-associated in monocytes; moreover, steady-state mRNA levels are present in unstimulated monocytes without translation into IL-32 protein, similar to other cytokines lacking a signal peptide. IL-32 production induced by M. tuberculosis is dependent on endogenous interferon-gamma (IFN gamma); endogenous IFN gamma is, in turn, dependent on M. tuberculosis-induced IL- 18 via caspase-1. Conclusions In conclusion, IL- 32 is a cell-associated proinflammatory cytokine, which is specifically stimulated by mycobacteria through a caspase-1- and IL- 18- dependent production of IFN gamma.
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