Endotoxin-induced expression of murine bactericidal permeability/increasing protein is mediated exclusively by toll/IL-1 receptor domain-containing adaptor inducing IFN-beta-dependent pathways.
Antimicrobial effector proteins are a key mechanism for the innate immune system to combat pathogens once they infect the host. We report the identification and cloning of the mouse homologue of human bactericidal permeability/increasing protein (BPI). Mouse BPI is constitutively expressed in lymphatic organs and tissues as well as in mouse testis. Upon stimulation with different TLR ligands, mouse BPI is strongly expressed in granulocytes and, surprisingly, in bone marrow-derived dendritic cells. Mouse BPI is most strongly induced by bacterial LPS through a signaling pathway that is completely dependent on TLR4-Toll/IL-1R domain-containing adaptor inducing IFN-beta. Functional studies revealed that mouse BPI does have the potential to neutralize LPS and inhibits bacterial growth. Mouse BPI is expressed in granulocytes and bone marrow-derived dendritic cells, and the transcriptional activation is controlled by TLRs.
Eckert
Melanie
M
Institute for Clinical Microbiology, Immunology, and Hygiene, University of Erlangen-Nuremberg, Erlangen, Germany.
Wittmann
Irene
I
Röllinghoff
Martin
M
Gessner
André
A
Schnare
Markus
M
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology; D033942:Adaptor Proteins, Vesicular Transport / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D015152:Blotting, Northern; D001854:Bone Marrow Cells / Q000276:immunology; D003001:Cloning, Molecular; D003713:Dendritic Cells / Q000276:immunology; D004731:Endotoxins / Q000378:metabolism*; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016899:Interferon-beta / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger / Q000032:analysis; D017472:Receptors, Interleukin-1 / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012480:Salmonella Infections / Q000276:immunology; D012486:Salmonella typhimurium / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D004731:Endotoxins; D016899:Interferon-beta; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors; C507779:MYD88 protein, human; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse; C021623:bactericidal permeability increasing protein