Expression of Toll-like Receptors on the Macrophages Activated by Bacterial Superantigens / 감염과화학요법

ABSTRACT

BACKGROUND: Staphylococcal enterotoxin B (SEB) as a prototype superantigen is known to play a pivotal role in toxic shock syndrome and severe sepsis. However, the precise mechanism initiating the activation of innate effector cells by SEB is unclear. Recently, Toll-like receptors (TLRs), the sensor of pathogen associated molecular pattern (PAMP), have been reported to be expressed abundantly in monocytic lineage-cells. The purpose of this study is to investigate whether TLRs are involved in the SEB-induced immune cell activation and to prove the differential TLRs expression in response to SEB and/or lipopolysaccharide (LPS). MATERIALS AND METHODS: SEB was purified by dye ligand affinity chromatography. The mRNA expression of TLR1-9 in human peripheral blood mononuclear cells (PBMC) and human monocyte- like THP-1 cell line stimulated by SEB and/or LPS was detected by RT-PCR. RESULTS: The treatment of PBMC with SEB elicited significant changes in the expression of several TLRs. Interestingly, the mRNAs of TLR1 and TLR5 were clearly up-regulated in PBMC, whereas mRNA of TLR4 was down-regulated in the very early period of stimulation within 1-2 hours, and subsequently up-regulated 3 hours later after the stimulation. The up-regulation of mRNA of TLR4 was detected in PBMC stimulated by LPS. The up-regulation was more prominent in the cells exposed concomitantly to SEB and LPS. The mRNA expression pattern of TLR4 in THP-1 cell line stimulated by SEB or LPS was comparable to those of PBMC. CONCLUSION: This study indicates that SEB triggers inflammatory signals on macrophages and PBMC by engaging TLRs, particularly TLR4. The combination of LPS and SEB synergistically modulates TLR4 signaling.