Bacterial lipoprotein induces tolerance in human THP-1 monocytes with reduced tumour necrosis factor α production via a CD14-independent pathway

Abstract

Abstract Background Endotoxin (lipopolysaccharide; LPS) tolerance is characterized by diminished production of tumour necrosis factor (TNF) α during prolonged exposure to LPS, and therefore represents an essential control mechanism during sepsis. However, it is unknown whether bacterial lipoprotein (BLP), another major component of bacterial walls, can cause tolerance. This study sought to determine whether BLP pretreatment can induce tolerance in human THP-1 monocytes. Methods Human THP-1 monocytic cells were pretreated with culture medium alone and medium containing LPS 10 ng ml−1 or BLP 10 ng ml−1 for 24 h. Cells were further stimulated with high doses (0·1–1 mg ml−1) of LPS or BLP for 6 h. TNF-α levels were determined by enzyme-linked immunosorbent assay. CD14 receptor expression on THP-1 monocytes was assessed by flow cytometry. Results When THP-1 cells were incubated with culture medium, BLP stimulation resulted in much higher TNF-α levels than LPS stimulation (P < 0·05). Following LPS pretreatment, LPS stimulation-induced TNF-α production was significantly attenuated, whereas BLP stimulation still produced a small amount of TNF-α. However, BLP pretreatment prevented both LPS and BLP stimulation-induced TNF-α production from THP-1 cells. FACScan analysis revealed that THP-1 monocytes do not express CD14 receptor. Conclusion These results demonstrate that BLP has a more potent effect than LPS on THP-1 monocyte TNF-α production. Furthermore, BLP pretreatment is capable of inducing both BLP as well as LPS tolerance via a CD14-independent pathway, indicating a unique ability to cause cross-tolerance.