Activation of angiogenin expression in macrophages by lipopolysaccharide via the TLR4/NF- κB pathway in colitis

Acta Biochim Biophys Sin (Shanghai). 2024 Apr 3. doi: 10.3724/abbs.2024013. Online ahead of print.ABSTRACTInflammatory bowel disease (IBD) is a debilitating condition that can lead to life-threatening complications. Macrophages are crucial in IBD management because they secrete various cytokines and regulate tissue repair. Macrophage-derived angiogenin (ANG) has been shown to be essential for limiting colonic inflammation, but its upstream regulatory pathway and role in macrophages remain unclear. Here we show that ANG expression is up-regulated in macrophages during colitis treatment or upon lipopolysaccharides (LPS) treatment. Mechanistically, LPS activates Toll-like receptor 4 (TLR4) to initiate NF-κB translocation from the cytoplasm to the nucleus, where it binds to the ANG promoter and enhances its transcriptional activity, leading to increased ANG expression. Interestingly, our data also reveal that the deletion of ANG in macrophages has no adverse effect on key macrophage functions, such as phagocytosis, chemotaxis, and cell survival. Our findings establish a "LPS-TLR4-NF-κB-ANG" regulatory axis in inflammatory disorders and confirm that ANG controls inflammation in a paracrine manner, highlighting the importance of ANG as a key mediator in the complex network of inflammatory processes.PMID:38567413 | DOI:10.3724/abbs.2024013
Source: Acta Biochimica et Biophysica Sinica - Category: Biochemistry Authors: Source Type: research