Toll-like receptors types 2 and 6 and the apoptotic process in human neutrophils

Abstract

Neutrophils (PMN) apoptosis plays an important role in limiting the last phase of inflammatory processes. It is unknown whether Toll-like receptor (TLR)2 acts independently or together with TLR6 in this process. The aim of this study was to estimate the relationship between the expressions of TLR2 and TLR6 and the apoptosis of human neutrophils in physiological conditions. We investigated the influence of recombinant human interleukin (IL)-18 and N-formyl-metionyl-leucyl-phenylalanine (fMLP) on the relationships between these receptors and neutrophil apoptosis. Our results showed that after 4-h incubation, the percentage of apoptotic PMNs significantly increased compared with PMN counts before incubation. The stronger expression of TLR2 on the neutrophils suggests that this receptor contributes more significantly to the induction of PMN apoptosis than does TLR6. We also demonstrated an influence of recombinant human IL-18 (rhIL-18) on the expression of TLR6, whereas this effect was not observed in the expression of TLR2. We observed that both rhIL-18 and fMLP inhibited the apoptosis of PMNs and that rhIL-18 had a stronger effect than fMLP. The obtained results suggest that not only TLR2, but also TLR6 plays an important role in the regulation of the apoptosis of PMNs. Changes in the expression of TLR6 and inhibition of apoptosis of PMNs by rhIL-18 seem to confirm the vital role this receptor and of rhIL-18 in regulating the survival of these cells. These data can be useful in developing methods to regulate PMN apoptosis in conditions associated with their excessive and unfavorable activation.