The Lip lipoprotein from Neisseria gonorrhoeae stimulates cytokine release and NF-kappaB activation in epithelial cells in a Toll-like receptor 2-dependent manner.
The human pathogen Neisseria gonorrhoeae produces an array of diseases ranging from urethritis to disseminated gonococcal infections. Early events in the establishment of infection involve interactions between N. gonorrhoeae and the mucosal epithelium, which leads to the local release of inflammatory mediators. Because of this, it is important to identify the bacterial virulence factors and host cell components that contribute to inflammation. Using a series of column chromatography steps, we purified a lipoprotein from N. gonorrhoeae strain F62 called Lip. This outer membrane antigen expresses a conserved epitope known as H.8, which is common to all pathogenic Neisseria species. We found the purified preparation of Lip to be a potent inflammatory mediator capable of inducing the release of the chemokine interleukin (IL)-8 and the cytokine IL-6 by immortalized human endocervical epithelial cells and the production of IL-8 and the activation of the transcription factor NF-kappaB by human embryonic kidney 293 (HEK) cells transfected with toll-like receptor (TLR) 2. Upon removal of Lip by immunoprecipitation, the ability of the H.8/Lip preparation to stimulate NF-kappaB activation was abolished. In addition to TLR2, the activation of NF-kappaB by H.8/Lip in HEK cells was enhanced upon coexpression of TLR1 but not TLR6. These observations provide evidence that Lip is capable of inducing the release of inflammatory mediators from epithelial cells in a TLR2-dependent manner.
Fisette
Philip L
PL
Division of Infectious Diseases, Department of Physiology and Biophysics, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, USA.
Ram
Sanjay
S
Andersen
Jorunn M
JM
Guo
Wen
W
Ingalls
Robin R
RR
D001425:Bacterial Outer Membrane Proteins / Q000276:immunology* / Q000302:isolation & purification; D001426:Bacterial Proteins / Q000276:immunology / Q000302:isolation & purification; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D007111:Immunity, Cellular; D018836:Inflammation Mediators / Q000276:immunology / Q000302:isolation & purification; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008074:Lipoproteins / Q000276:immunology / Q000302:isolation & purification; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D009344:Neisseria gonorrhoeae / Q000276:immunology / Q000472:pathogenicity*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014162:Transfection
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; C079135:Lip antigen; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors