Inhibition of Bruton's TK regulates macrophage NF-κB and NLRP3 inflammasome activation in metabolic inflammation.

ABSTRACT:

Background and purpose

There are no medications currently available to treat metabolic inflammation. Bruton's tyrosine kinase (BTK) is highly expressed in monocytes and macrophages and regulates NF-κB and NLRP3 inflammasome activity; both propagate metabolic inflammation in diet-induced obesity.

Experimental approach

Using an in vivo model of chronic inflammation, high-fat diet (HFD) feeding, in male C57BL/6J mice and in vitro assays in primary murine and human macrophages, we investigated if ibrutinib, an FDA approved BTK inhibitor, may represent a novel anti-inflammatory medication to treat metabolic inflammation.

Key results

HFD-feeding was associated with increased BTK expression and activation, which was significantly correlated with monocyte/macrophage accumulat

SUBMITTER: Purvis GSD 

PROVIDER: S-EPMC7484557 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature