Abstract

The adipokine leptin elicits changes in the expression of
the activation markers CD40 and CD69 in PBMCs and
DCs, yet its effect on PRRs remains to be elucidated.
Serum leptin concentrations are elevated in obesity and
T2DM, which are both diseases associated with a proinflammatory
state. We therefore investigated a possible
role for leptin in monocyte TLR and CD14 expression.
Leptin increased TLR2 cell-surface and mRNA expression
in THP-1 and primary human monocytes. In
contrast, leptin had no effect on monocyte TLR4 expression
in THP-1 or primary monocytes. CD14 cell-surface
and mRNA expression were increased after leptin
stimulation in THP-1 monocytes. However, no change in
cell-surface CD14 expression was observed after leptin
treatment in primary human monocytes. Leptin also upregulated
the expression of PU.1 and EGR2, transcription
factors involved in myeloid cell differentiation. Additionally,
leptin potentiated Escherichia coli and Porphyromonas
gingivalis LPS-induced TNF-� secretion in
THP-1 monocytes. In conclusion, we show that leptin
and LPS differentially influence monocyte phenotype
and demonstrate, for the first time, a regulatory effect
of leptin on the monocyte expression of TLR2. Leptinstimulated
TLR2 expression may potentiate innate immunity
and inflammation in conditions of hyperleptinemia,
such as obesity and T2DM.