The production of secretory leukocyte protease inhibitor by dendritic cells.
Secretory leukocyte protease inhibitor (SLPI) is produced at mucosal sites where it plays an important role in the homeostatic control of local inflammation. In addition to its anti-protease activity SLPI is able to reduce LPS activity by interfering with the transfer of LPS to CD14. In addition SLPI can be taken up by cells where it can prevent signaling via the NF-κB route. It is preferentially expressed in dendritic cells from mucosal sites, suggesting a role in the maintenance of a tolerogenic environment, but it is unclear how this differential expression is regulated. Here we analyzed the regulation of SLPI expression in dendritic cells and found that activation by TLR ligands but not via antiCD40 leads to its expression, which is predominantly dependent on p38 activation. This induced expression is late compared to the induction of cytokines and co-stimulatory molecules, is not dependent on factors that are secreted by the cell itself and may be related to cellular feedback mechanisms involved in inflammation and immunity. In correlation with the differential expression by TLR ligands and antiCD40, SLPI deficient mice show enhanced specific immunity when antigen is co-injected with LPS, but not with antiCD40. The results underscore the importance of SLPI as a modulator of specific immunity that can also function at peripheral sites under pathogenic pressure.
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Aram B
AB
Vroling
Tanja
T
Konijn
Janneke N
JN
Samsom
Georg
G
Kraal
D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D003713:Dendritic Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D016328:NF-kappa B / Q000378:metabolism; D017433:Protein Structure, Secondary; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D008070:Lipopolysaccharides; D016328:NF-kappa B; D053481:Secretory Leukocyte Peptidase Inhibitor; D048051:p38 Mitogen-Activated Protein Kinases