AI Article Synopsis
- NHE1, a sodium/hydrogen exchanger, plays a crucial role in inflammatory cells, but its regulation in activated cells is not well understood.
- Research using the RAW 264 macrophage-like cell line revealed that the TLR4 ligand lipopolysaccharide (LPS) decreases NHE1 levels and activity, alongside other TLR ligands like zymosan A and poly(I:C).
- The study concluded that LPS induces NHE1 ubiquitination and decreases CHP1 expression through JNK activation, with results suggesting involvement of the ubiquitin-proteasome system in NHE1 down-regulation.
Article Abstract
The role of Na/H exchanger 1 (NHE1) in various cell types, including inflammatory cells, has been extensively studied. However, regulation of NHE1 protein level in activated inflammatory cells is yet to be characterized. In this study, we investigated whether Toll-like receptor (TLR) ligands can regulate NHE1 protein level in the mouse macrophage-like RAW 264 cell line. We found that lipopolysaccharide (LPS), a TLR4 ligand, lowered NHE1 level and activity in RAW 264 cells and in primary murine macrophages. Other TLR ligands, such as zymosan A and poly(I:C), also displayed reduced NHE1 level. LPS promoted NHE1 ubiquitination and reduced the expression of calcineurin homologous protein 1 (CHP1), a regulator of NHE1 activity and stability. These responses were inhibited by c-Jun N-terminal kinase (JNK) inhibitor SP600125 and dexamethasone. A proteasome inhibitor, but not caspase-3 or lysosomal inhibitors, blocked the LPS-induced NHE1 down-regulation. These results suggested that LPS promotes the degranulation of NHE1 mediated by the ubiquitin-proteasome system and CHP1 downregulation resulting from activation of JNK.
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| http://dx.doi.org/10.1016/j.imbio.2016.10.005 | DOI Listing |
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