CXCL4 and CXCL4L1 activate human macrophage via TLR4 signaling to modulate inflammatory responses.

ABSTRACT: The chemokine CXCL4 activates human monocytes/macrophages and contributes to the pathogenesis of inflammatory and fibrotic diseases. However, the receptor of CXCL4, CXCR3, is not expressed in human monocytes/macrophages. Thus, signaling pathways and receptors that mediate human monocytes/macrophages response to CXCL4 alone are not well characterized. Using human primary monocytes and mouse bone marrow-derived macrophages, we reported that CXCL4 activated NF-κB and a TBK1-JNK-AP1 signaling axis that drove the expression of inflammatory, fibrotic and neutrophil chemokine genes, and also a TRIF-RIPK3 axis-dependent necroptosis in primary human monocytes. Surprisingly, multiple evidence targeting TLR4 expression and function suggested a role for TLR4 in CXCL4 responses. Further, we show that C

SUBMITTER: Bai H 

PROVIDER: S-EPMC12720328 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature