The role of lipopolysaccharide, pro-inflammatory cytokines and bacterial superantigens in the transcriptional regulation of lymphotoxin alpha and beta in mouse splenocytes

Cytokine. 1998 Dec;10(12):940-7. doi: 10.1006/cyto.1998.0386.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics
  • Aging / immunology
  • Animals
  • Base Sequence
  • Concanavalin A / pharmacology
  • Cytokines / pharmacology
  • DNA Primers / genetics
  • In Vitro Techniques
  • Inflammation Mediators / pharmacology
  • Lipopolysaccharides / pharmacology
  • Lymphotoxin-alpha / genetics*
  • Lymphotoxin-beta
  • Membrane Proteins / genetics*
  • Mice
  • Mice, Inbred BALB C
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sepsis / genetics
  • Sepsis / immunology
  • Spleen / drug effects
  • Spleen / metabolism
  • Superantigens / physiology
  • Transcription, Genetic / drug effects
  • Up-Regulation / drug effects

Substances

  • Cytokines
  • DNA Primers
  • Inflammation Mediators
  • Lipopolysaccharides
  • Ltb protein, mouse
  • Lymphotoxin-alpha
  • Lymphotoxin-beta
  • Membrane Proteins
  • RNA, Messenger
  • Superantigens
  • Concanavalin A