Inhibitors of DAG metabolism suppress CCR2 signalling in human monocytes.

ABSTRACT:

Background and purpose

CCL2 is an inflammatory chemokine that stimulates the recruitment of monocytes into tissue via activation of the GPCR CCR2.

Experimental approach

Freshly isolated human monocytes and THP-1 cells were used. Fura-2 loaded cells were used to measure intracellular Ca²⁺ responses. Transwell migration to measure chemotaxis. siRNA-mediated gene knock-down was used to support pharmacological approaches.

Key results

CCL2 evoked intracellular Ca²⁺ signals and stimulated migration in THP-1 monocytic cells and human CD14⁺ monocytes in a CCR2-dependent fashion. Attenuation of DAG catabolism in monocytes by inhibiting DAG kinase (R59949) or DAG lipase (RHC80267) activity suppressed CCL2-evoked Ca²⁺ signalling and tr

SUBMITTER: Day P 

PROVIDER: S-EPMC6609539 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature