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Connexin43 Is Required for the Effective Activation of Spleen Cells and Immunoglobulin Production
Gap junctions (Gjs), formed by specific protein termed connexins (Cxs), regulate many important cellular processes in cellular immunity. However, little is known about their effects on humoral immunity. Here we tested whether and how Gj protein connexin43 (Cx43) affected antibody production in splee...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888161/ https://www.ncbi.nlm.nih.gov/pubmed/31752090 http://dx.doi.org/10.3390/ijms20225789 |
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author | Huang, Yanru Mao, Zhimin Zhang, Xiling Yang, Xiawen Sawada, Norifumi Takeda, Masayuki Yao, Jian |
author_facet | Huang, Yanru Mao, Zhimin Zhang, Xiling Yang, Xiawen Sawada, Norifumi Takeda, Masayuki Yao, Jian |
author_sort | Huang, Yanru |
collection | PubMed |
description | Gap junctions (Gjs), formed by specific protein termed connexins (Cxs), regulate many important cellular processes in cellular immunity. However, little is known about their effects on humoral immunity. Here we tested whether and how Gj protein connexin43 (Cx43) affected antibody production in spleen cells. Detection of IgG in mouse tissues and serum revealed that wild-type (Cx43(+/+)) mouse had a significantly higher level of IgG than Cx43 heterozygous (Cx43(+/−)) mouse. Consistently, spleen cells from Cx43(+/+) mouse produced more IgG under both basal and lipopolysaccharide (LPS)-stimulated conditions. Further analysis showed that LPS induced a more dramatic activation of ERK and cell proliferation in Cx43(+/+) spleen cells, which was associated with a higher pro-oxidative state, as indicated by the increased NADPH oxidase 2 (NOX2), TXNIP, p38 activation and protein carbonylation. In support of a role of the oxidative state in the control of lymphocyte activation, exposure of spleen cells to exogenous superoxide induced Cx43 expression, p38 activation and IgG production. On the contrary, inhibition of NOX attenuated the effects of LPS. Collectively, our study characterized Cx43 as a novel molecule involved in the control of spleen cell activation and IgG production. Targeting Cx43 could be developed to treat certain antibody-related immune diseases. |
format | Online Article Text |
id | pubmed-6888161 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68881612019-12-09 Connexin43 Is Required for the Effective Activation of Spleen Cells and Immunoglobulin Production Huang, Yanru Mao, Zhimin Zhang, Xiling Yang, Xiawen Sawada, Norifumi Takeda, Masayuki Yao, Jian Int J Mol Sci Article Gap junctions (Gjs), formed by specific protein termed connexins (Cxs), regulate many important cellular processes in cellular immunity. However, little is known about their effects on humoral immunity. Here we tested whether and how Gj protein connexin43 (Cx43) affected antibody production in spleen cells. Detection of IgG in mouse tissues and serum revealed that wild-type (Cx43(+/+)) mouse had a significantly higher level of IgG than Cx43 heterozygous (Cx43(+/−)) mouse. Consistently, spleen cells from Cx43(+/+) mouse produced more IgG under both basal and lipopolysaccharide (LPS)-stimulated conditions. Further analysis showed that LPS induced a more dramatic activation of ERK and cell proliferation in Cx43(+/+) spleen cells, which was associated with a higher pro-oxidative state, as indicated by the increased NADPH oxidase 2 (NOX2), TXNIP, p38 activation and protein carbonylation. In support of a role of the oxidative state in the control of lymphocyte activation, exposure of spleen cells to exogenous superoxide induced Cx43 expression, p38 activation and IgG production. On the contrary, inhibition of NOX attenuated the effects of LPS. Collectively, our study characterized Cx43 as a novel molecule involved in the control of spleen cell activation and IgG production. Targeting Cx43 could be developed to treat certain antibody-related immune diseases. MDPI 2019-11-18 /pmc/articles/PMC6888161/ /pubmed/31752090 http://dx.doi.org/10.3390/ijms20225789 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Huang, Yanru Mao, Zhimin Zhang, Xiling Yang, Xiawen Sawada, Norifumi Takeda, Masayuki Yao, Jian Connexin43 Is Required for the Effective Activation of Spleen Cells and Immunoglobulin Production |
title | Connexin43 Is Required for the Effective Activation of Spleen Cells and Immunoglobulin Production |
title_full | Connexin43 Is Required for the Effective Activation of Spleen Cells and Immunoglobulin Production |
title_fullStr | Connexin43 Is Required for the Effective Activation of Spleen Cells and Immunoglobulin Production |
title_full_unstemmed | Connexin43 Is Required for the Effective Activation of Spleen Cells and Immunoglobulin Production |
title_short | Connexin43 Is Required for the Effective Activation of Spleen Cells and Immunoglobulin Production |
title_sort | connexin43 is required for the effective activation of spleen cells and immunoglobulin production |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888161/ https://www.ncbi.nlm.nih.gov/pubmed/31752090 http://dx.doi.org/10.3390/ijms20225789 |
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