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The regulation of Na+/H+ exchangers by Toll-like receptors under inflammation

CHE Hao, RUAN Yu-Yan, LUO Tang-Yan, CHEN Ming-Min^*

Medical School, Shaoxing University, Shaoxing 312000, China

Abstract

Toll-like receptors (TLRs) can be recognized and activated by different pathogen associated molecular patterns (PAMPs), which induce innate immune response and inflammation of the body. Na+/H+ exchangers (NHEs) not only play roles in the regulation of cellular pH and cell volume, maintenance of the cavity microenvironment and nutrients absorption, but also are related to cell proliferation, migration and apoptosis. The activity and membrane protein expression of NHEs are inhibited under the inflammation condition. It has been shown that the activation of TLR2 in colon epithelial cells can inhibit the activity of NHE1 through MyD88 independent pathway, which involves the recruitment of Src and the phosphorylation of PI3Ks. Other studies on intestinal macrophage showed long-term LPS stimulation can induce TLR4 activation through MyD88-dependent pathway (TLR4/MyD88/NF-κB) and induce inflammation and degeneration of intracellular NHE1, which leads to NHE1 activity inhibition. But short-term LPS exposure increases the activity and protein expression of NHE1. The activation of TLR5 increases the activity of NHE3. The activity and/or expression of NHE3 in intestinal macrophages in colitis patients and model animals were decreased. In renal tubular epithelial cells, basolateral LPS stimulation inhibits luminal NHE3 activation through TLR4/MyD88-dependent MAPK/ERK signaling pathway. And LPS stimulation on the lumen side activates TLR4/MyD88-dependent PI3K-AKT-mTOR signaling pathway, which results in the inhibition of NHE1 activity in basolateral side, and then affects the NHE3 function of the lumen side.

Key words: Toll-like receptors; Na+/H+ exchanger; infection; inflammatory bowel disease

Received: 2018-05-24　　Accepted: 2018-10-24

Corresponding author: 陈明敏　　E-mail: ellechen80@hotmail.com

DOI: 10.13294/j.aps.2018.0069

Citing This Article：

CHE Hao, RUAN Yu-Yan, LUO Tang-Yan, CHEN Ming-Min. The regulation of Na+/H+ exchangers by Toll-like receptors under inflammation. Acta Physiol Sin 2018; 70 (5): 521-530 (in Chinese with English abstract).