THE ROLE OF LIPOPOLYSACCHARIDE, PRO-INFLAMMATORY CYTOKINES AND BACTERIAL SUPERANTIGENS IN THE TRANSCRIPTIONAL REGULATION OF LYMPHOTOXIN α AND β IN MOUSE SPLENOCYTES

Abstract

Lymphotoxin α (LT-α) and lymphotoxin β (LT-β) 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-α and LT-β 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-α mRNA expression in vitro in murine cells. Basal expression of LT-β 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-β transcript, sepsis-associated mediators did not affect its regulation. Neither the pro-inflammatory cytokines interleukin 2 (IL-2), TNF-α nor LPS alone or in combination with interferon γ (IFN-γ) had any effect on LT-β mRNA expression. The bacterial superantigens TSST-1, SEB and streptococcal pyrogenic exotoxin A (SPEA) were also unable to upregulate LT-β mRNA transcript, in contrast to the observation with LT-α.