期刊
PHARMACOLOGICAL RESEARCH
卷 177, 期 -, 页码 -出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2022.106112
关键词
Voltage-gated potassium channel; Interferon; Toll receptor; Kv channel; Innate immunity
资金
- National Natural Science Foundation of China [81973333]
- Young Scholars of Pearl River in Guangdong Province [2019A1515010964, 2021A1515011054]
- Natural Science Foundation of Guangdong Province
Potassium efflux mediated by the Kv1.3 channel plays a critical role in TLR3/4 activation, and pharmacological inhibition of Kv1.3 may be beneficial for treating autoimmune diseases and bacterial infections.
Emerging data have demonstrated the critical roles of potassium efflux in the innate immune system. However, the role of potassium efflux in TLR3/4 activation and type I interferon (IFN) responses are not well elucidated. In the present study, we found potassium efflux is essential for TLR3/4 signaling, which mediates the expression of IFN and its inducible gene Cxcl10 and proinflammatory cytokine gene TNF-alpha. Furthermore, pharmacological inhibition of Kv1.3 channel (PAP-1), but not Kir2.1, KCa3.1 or TWIK2, attenuated TLR3/4 receptor activation in macrophages. Mechanistically, PAP-1 suppressed LPS-induced inflammatory function through marked suppressing the activation of JNK mitogen-activated protein kinase (MAPK) and p65 subunit of nuclear factor-kB (NF-kB). Notably, PAP-1 effectively protected mice against Listeria monocytogenes induced infection. Our findings reveal that potassium efflux mediated by the Kv1.3 channel is essential for TLR3/4 activation and suggest that pharmacological inhibition of Kv1.3 may help to treat type I IFN related autoimmune diseases and bacterial infections.
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