Co-regulated decrease of neurokinin-1 receptor and hemokinin-1 gene expression in monocytes and macrophages after activation with pro-inflammatory cytokines

Hemokinin-1 (HK-1), a potent ligand for the Neurokinin-1 receptor (NK-1) is thought to play a role in the immune system. To investigate the regulation of this receptor-ligand pair, we examined the effects of pro-inflammatory cytokines on their expression in the monocyte/macrophage cell lines Wehi-3 and RAW264.7. We demonstrate co-expression of NK-1 and HK-1 mRNA in both lines, as well as functional NK-1 receptor protein in Wehi-3 cells. Stimulation with IFN-gamma, IL-1 beta and TNF-alpha markedly decreased NK-1 and HK-1 mRNA as well as NK-1 receptor protein, which coincided with monocytic differentiation. A co-regulated decrease could also be observed in differentiating primary bone marrow macrophages, suggesting that this receptor-ligand pair may be controlled by cytokine networks and may serve a developmental role in the immune system. (c) 2007 Elsevier B.V. All rights reserved.