KCa3.1 inhibition-induced activation of the JNK/c-Jun signaling pathway enhances IL-10 expression in peripherally-induced regulatory T cells

Miki Matsui; Junko Kajikuri; Kyoko Endo; Hiroaki Kito; Susumu Ohya

doi:10.1016/j.jphs.2021.09.007

K_Ca3.1 inhibition-induced activation of the JNK/c-Jun signaling pathway enhances IL-10 expression in peripherally-induced regulatory T cells

J Pharmacol Sci. 2022 Jan;148(1):1-5. doi: 10.1016/j.jphs.2021.09.007. Epub 2021 Oct 1.

Authors

Miki Matsui¹, Junko Kajikuri¹, Kyoko Endo¹, Hiroaki Kito¹, Susumu Ohya²

Affiliations

¹ Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan.
² Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan. Electronic address: sohya@med.nagoya-cu.ac.jp.

PMID: 34924112
DOI: 10.1016/j.jphs.2021.09.007

Abstract

The K_Ca3.1 inhibition up-regulates IL-10 expression in regulatory T (T_reg) cells in the recovery phase of inflammatory bowel disease (IBD) model mice; however, the underlying signaling pathway remains unclear. We investigated the involvement of AP-1 (Fos/Jun) and NF-κB in the expression of IL-10 and its transcription factors (TFs) in in vitro-induced mouse splenic T_reg cells. The pharmacological inhibition of JNK reversed K_Ca3.1 inhibition-induced increases in the expression of IL-10 and its TFs. The inhibition of K_Ca3.1 increased phosphorylated JNK and c-Jun levels. Therefore, the JNK/c-Jun signaling pathway may contribute to the K_Ca3.1 inhibition-induced up-regulation of IL-10 in peripherally-induced T_reg cells.

Keywords: IL-10; JNK/c-Jun; K(Ca)3.1.

MeSH terms

Animals
Disease Models, Animal
Gene Expression / genetics*
Inflammatory Bowel Diseases / genetics*
Interleukin-10 / genetics*
Interleukin-10 / metabolism*
Intermediate-Conductance Calcium-Activated Potassium Channels / antagonists & inhibitors*
Intermediate-Conductance Calcium-Activated Potassium Channels / physiology*
JNK Mitogen-Activated Protein Kinases / metabolism*
MAP Kinase Signaling System / genetics*
MAP Kinase Signaling System / physiology*
Mice
NF-kappa B / metabolism
Phosphorylation
Proto-Oncogene Proteins c-jun / metabolism*
T-Lymphocytes, Regulatory / metabolism*
Transcription Factor AP-1 / metabolism
Transcription Factors / genetics
Transcription Factors / metabolism

Substances

IL10 protein, mouse
Intermediate-Conductance Calcium-Activated Potassium Channels
Kcnn4 protein, mouse
NF-kappa B
Proto-Oncogene Proteins c-jun
Transcription Factor AP-1
Transcription Factors
Interleukin-10
JNK Mitogen-Activated Protein Kinases