Pneumococcal cell wall activates NF-kappa B in human monocytes: aspects distinct from endotoxin.
The transcription factor NF-kappa B plays a central role in inflammation by controlling the transcription of multiple genes which participate in the acute phase response. Mice with a targeted disruption of the p50 subunit of NF-kappa B are hyper-susceptible to challenge with pneumococci but not endotoxin. We sought to clarify the role of NF-kappa B in the host response to the critical inflammatory component of pneumococci, the cell wall. Activation of NF-kappa B was monitored by expression of luciferase from cells transfected with an NF-kappa B dependent luciferase reporter construct. 70Z/3 murine pre-B cells and U937 human monocytes failed to produce luciferase in response to 10(7) pneumococci or 10 mu g cell wall; strong responses were obtained with lO mu g of LPS. In contrast, THP-1 human monocytes showed strong luciferase production with all three stimuli: LPS, intact pneumococci and cell wall. The response was time and dose dependent. Cell wall activity was retained despite alteration of the choline of the teichoic acid or protease treatment suggesting the glycopeptide backbone to be a critical determinant of bioactivity. We conclude that activation of NF-kappa B by pneumococci is restricted to certain cells and that this proinflammatory activity may be a specific feature of the pneumococcal cell wall glycopeptide backbone.
Spellerberg
B
B
Laboratory of Molecular Infectious Diseases, Rockefeller University, New York, NY 10021, USA.
Rosenow
C
C
Sha
W
W
Tuomanen
E I
EI
D000818:Animals; D002460:Cell Line; D002473:Cell Wall / Q000378:metabolism; D004731:Endotoxins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology*; D016328:NF-kappa B / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000378:metabolism*
D004731:Endotoxins; D016328:NF-kappa B