Histamine increases the expression of LOX-1 via H2 receptor in human monocytic THP-1 cells

Abstract

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a member of the scavenger receptor family, and is known to be expressed in monocytes/macrophages. We investigated the effect of histamine on the expression of LOX-1 in cells of the human monocytic leukemia cell line THP-1. Histamine as well as forskolin and dibutyryl cyclic AMP (Bt2-cAMP) stimulated the THP-1 monocytes to express the LOX-1 gene at the transcription level. This histamine effect on LOX-1 gene expression, via the histamine H2 receptor-mediated cAMP signal transduction pathway, was reduced after differentiation of the cells into macrophages, even though forskolin and Bt2-cAMP still enhanced the gene expression. The alteration of the responsiveness of LOX-1 expression to histamine was related to suppressed expression of the H2 receptor in THP-1 macrophages. The switch of the predominant class of histamine receptors between H1 and H2 would modulate the effects of histamine on LOX-1 gene expression in monocytes and macrophages, and therefore, would play a certain role in the inflammatory aspects of atherogenesis.