The role of lipopolysaccharide, pro-inflammatory cytokines and bacterial superantigens in the transcriptional regulation of lymphotoxin alpha and beta in mouse splenocytes.
Lymphotoxin alpha (LT-alpha) and lymphotoxin beta (LT-beta) are members of the tumour necrosis factor (TNF) ligand family. Because of the importance of TNF in the pathogenesis of septic shock, the expression of LT-alpha and LT-beta mRNA in murine splenocytes stimulated with different pro-inflammatory cytokines, sepsis-associated mediators such as lipopolysaccharide (LPS) and bacterial superantigens was investigated. The authors show that the bacterial superantigens, toxic shock syndrome toxin 1 (TSST-1) and staphylococcal enterotoxin B (SEB) upregulate LT-alpha mRNA expression in vitro in murine cells. Basal expression of LT-beta mRNA was found in unstimulated murine splenocytes, and could be increased by the addition of the mitogen concanavalin A (Con A). Despite this suggested inducibility of the murine LT-beta transcript, sepsis-associated mediators did not affect its regulation. Neither the pro-inflammatory cytokines interleukin 2 (IL-2), TNF-alpha nor LPS alone or in combination with interferon gamma (IFN-gamma) had any effect on LT-beta mRNA expression. The bacterial superantigens TSST-1, SEB and streptococcal pyrogenic exotoxin A (SPEA) were also unable to upregulate LT-beta mRNA transcript, in contrast to the observation with LT-alpha.
Department of Infectious Diseases, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
M
M
Zinetti
S
S
Agyekum
T
T
Evans
J
J
Polak
J
J
Cohen
D000375:Aging / Q000235:genetics / Q000276:immunology; D000818:Animals; D001483:Base Sequence; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008233:Lymphotoxin-alpha / Q000235:genetics*; D053308:Lymphotoxin-beta; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D018089:Superantigens / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D016207:Cytokines; D017931:DNA Primers; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C505887:Ltb protein, mouse; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D008565:Membrane Proteins; D012333:RNA, Messenger; D018089:Superantigens; D003208:Concanavalin A