title: Proteinase inhibitor-9 expression is induced by maturation in dendritic cells via p38 MAP kinase.
abstract: Dendritic cells (DC) are crucial for the induction of CD8(+) T cell responses. However, as DC present antigen, they may also be at risk for being killed by recent activated CD8+ T cells. Previously we have shown that lipopolysaccharide (LPS)- or CD40L-stimulated monocyte-derived DC express high levels of the granzyme B-inhibitory serpin proteinase inhibitor-9 (PI-9). Furthermore we found that its murine homolog serine protease inhibitor-6 (SPI-6) protected murine DC against cytotoxic T lymphocyte-induced apoptosis. These data suggest that PI-9/SPI-6 may regulate survival of DC when they are under attack by effector cells. We therefore analyzed how PI-9 is regulated upon stimulation with several Toll-like receptor ligands. We found that the expression of PI-9 correlated with maturation, as measured with CD86 levels, but not with the production of interleukin-12-p70. Using LPS as stimulus, we also showed that the induction of PI-9 is dependent on the p38 mitogen-activated protein kinase signaling pathway. The data suggest that PI-9 is tightly linked to maturation and may allow DC to exert their function in a potentially hostile environment.
authors.affiliation: Laboratory of Experimental Oncology and Radiobiology, Center of Experimental Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Michael
authors.initials: M
authors.lastname: Bots
authors.forename: Elza
authors.initials: E
authors.lastname: de Bruin
authors.forename: Mirjam T G A
authors.initials: MT
authors.lastname: Rademaker-Koot
authors.forename: Jan Paul
authors.initials: JP
authors.lastname: Medema
mesh_terms: D051940:B7-2 Antigen / Q000378:metabolism; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D053804:Granzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D015842:Serine Proteinase Inhibitors / Q000276:immunology / Q000378:metabolism; D015843:Serpins / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D051940:B7-2 Antigen; D008070:Lipopolysaccharides; C102316:SERPINB9 protein, human; D015842:Serine Proteinase Inhibitors; D015843:Serpins; D051193:Toll-Like Receptors; D018664:Interleukin-12; D048051:p38 Mitogen-Activated Protein Kinases; D053804:Granzymes