Lipopolysaccharide-binding protein down-regulates the expression of interleukin-6 by human gingival fibroblast

Lipopolysaccharide-binding protein (LBP) participates in the interaction of lipopolysacchaide (LPS) with CD14 to modulate the expression of cytokines. Human gingival fibroblast may actively participate in LPS-induced immuno-inflammatory responses through CD14, toll-like receptor (TLR) superfamily, MD-2 and related adaptive proteins, leading to the expression of cytokines.

The present in vitro study aimed to investigate the possible effect of LBP and E. coli LPS interaction on the expression of cellular LPS receptors and IL-6 by human gingival fibroblast.

The mRNA expression of CD14, LBP, TLR-2, TLR-4, MD-2 and IL-6 in human gingival fibroblast explants was detected by reverse transcriptionpolymerase chain reaction (RT-PCR) in the presence or absence of E. coli LPS and recombinant human LBP (rhLBP), while IL-6 peptides were analyzed by ELISA and immunohistochemistry, respectively.

Human gingival fibroblast could constitutively express CD14, MD-2 and IL-6 mRNAs, but not TLR-2, TLR-4 and LBP mRNAs. E. coli LPS induced the messages expression of MD-2, TLR-2 and -4. The expression of both IL-6 message and peptide was up-regulated by E. coli LPS in a dose dependent manner. Whereas rhLBP could significantly down-regulate the expression of both mRNAs and peptides of CD14 and IL-6 but not MD-2 signals in the presence or absence of E. coli LPS. The up-regulated expression of TLR-2 and -4 by E. coli LPS no longer existed in the presence of rhLBP.

This study suggests that LBP may down-regulate the expression of IL-6 by human gingival fibroblast. Further studies are warranted to clarify the molecular mechanisms of LBP in regulation of cytokine expression by host cells and to elaborate the relevant clinical implications.