The role of lipopolysaccharide pro-inflammatory cytokines and bacterial superantigens in the transcriptional regulation of lymphotoxin alpha and betain 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 o f TNF in the pathogenesis of septic shock, the expression of LT-alpha and L T-beta mRNA in murine splenocytes stimulated with different pro-inflammator y cytokines, sepsis-associated mediators such as lipopolysaccharide (LPS) a nd bacterial superantigens was investigated. The authors show that the bact erial superantigens, toxic shock syndrome toxin 1 (TSST-1) and staphylococc al enterotoxin B (SEB) upregulate LT-alpha mRNA expression in vitro in muri ne cells. Basal expression of LT-beta mRNA was found in unstimulated murine splenocytes, and could be increased by the addition of the mitogen concana valin A (Con A). Despite this suggested inducibility of the murine LT-beta transcript, sepsis-associated mediators did not affect its regulation. Neit her 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, SEE and strep tococcal pyrogenic exotoxin A (SPEA) were also unable to upregulate LT-beta mRNA transcript, in contrast to the observation with LT-alpha. (C) 1998 Ac ademic Press.