PMID- 30151015 OWN - NLM STAT- MEDLINE DCOM- 20181029 LR - 20231213 IS - 1689-1392 (Electronic) IS - 1425-8153 (Print) IS - 1425-8153 (Linking) VI - 23 DP - 2018 TI - Increased expression and functionality of the gap junction in peripheral blood lymphocytes is associated with hypertension-mediated inflammation in spontaneously hypertensive rats. PG - 40 LID - 10.1186/s11658-018-0106-0 [doi] LID - 40 AB - BACKGROUND: Imbalances in circulating T lymphocytes play critical roles in the pathogenesis of hypertension-mediated inflammation. Connexins (Cxs) in immune cells are involved in the maintenance of homeostasis of T lymphocytes. However, the association between Cxs in peripheral blood T lymphocytes and hypertension-mediated inflammation remains unknown. This study was designed to investigate the role of Cxs in T lymphocytes in hypertension-mediated inflammation in spontaneously hypertensive rats (SHRs). METHODS: The systolic blood pressure (SBP) in Wistar-Kyoto (WKY) rats and SHRs was monitored using the tail-cuff method. The serum cytokine level was determined using ELISA. The proportions of different T-lymphocyte subtypes in the peripheral blood, the expressions of Cx40/Cx43 in the T-cell subtypes, and the gap junctional intracellular communication (GJIC) of peripheral blood lymphocytes were measured using flow cytometry (FC). The accumulations of Cx40/Cx43 at the plasma membrane and/or in the cytoplasm were determined using immunofluorescence staining. The in vitro mRNA levels of cytokines and GJIC in the peripheral blood lymphocytes were respectively examined using real-time PCR and FC after treatment with Gap27 and/or concanavalin A (Con A). RESULTS: The percentage of CD4(+) T cells and the CD4(+)/CD8(+) ratio were high, and the accumulation or expressions of Cx40/Cx43 in the peripheral blood lymphocytes in SHRs were higher than in those of WKY rats. The percentage of CD8(+) and CD4(+)CD25(+) T cells was lower in SHRs. The serum levels of IL-2, IL-4 and IL-6 from SHRs were higher than those from WKY rats, and the serum levels of IL-2 and IL-6 positively correlated with the expression of Cx40/Cx43 in the peripheral blood T lymphocytes from SHRs. The peripheral blood lymphocytes of SHRs exhibited enhanced GJIC. Cx43-based channel inhibition, which was mediated by Gap27, remarkably reduced GJIC in lymphocytes, and suppressed IL-2 and IL-6 mRNA expressions in Con A stimulated peripheral blood lymphocytes. CONCLUSIONS: Our data suggest that Cxs may be involved in the regulation of T-lymphocyte homeostasis and the production of cytokines. A clear association was found between alterations in Cxs expression or in Cx43-based GJIC and hypertension-mediated inflammation. FAU - Ni, Xin AU - Ni X AD - 1Department of Physiology, Medical College of Shihezi University, 59 North 2nd Road, Shihezi, Xinjiang 832002 People's Republic of China. ISNI: 0000 0001 0514 4044. GRID: grid.411680.a AD - 2Key Laboratory of Xingjiang Endemic and Ethnic Diseases, Medical College of Shihezi University, Shihezi, Xinjiang China. ISNI: 0000 0001 0514 4044. GRID: grid.411680.a FAU - Li, Xin-Zhi AU - Li XZ AD - 3Department of Pathophysiology, Medical College of Shihezi University, Shihezi, Xinjiang China. ISNI: 0000 0001 0514 4044. GRID: grid.411680.a FAU - Fan, Zhi-Ru AU - Fan ZR AD - 1Department of Physiology, Medical College of Shihezi University, 59 North 2nd Road, Shihezi, Xinjiang 832002 People's Republic of China. ISNI: 0000 0001 0514 4044. GRID: grid.411680.a AD - 2Key Laboratory of Xingjiang Endemic and Ethnic Diseases, Medical College of Shihezi University, Shihezi, Xinjiang China. ISNI: 0000 0001 0514 4044. GRID: grid.411680.a FAU - Wang, Ai AU - Wang A AD - 1Department of Physiology, Medical College of Shihezi University, 59 North 2nd Road, Shihezi, Xinjiang 832002 People's Republic of China. ISNI: 0000 0001 0514 4044. GRID: grid.411680.a AD - 2Key Laboratory of Xingjiang Endemic and Ethnic Diseases, Medical College of Shihezi University, Shihezi, Xinjiang China. ISNI: 0000 0001 0514 4044. GRID: grid.411680.a FAU - Zhang, Hai-Chao AU - Zhang HC AD - 1Department of Physiology, Medical College of Shihezi University, 59 North 2nd Road, Shihezi, Xinjiang 832002 People's Republic of China. ISNI: 0000 0001 0514 4044. GRID: grid.411680.a AD - 2Key Laboratory of Xingjiang Endemic and Ethnic Diseases, Medical College of Shihezi University, Shihezi, Xinjiang China. ISNI: 0000 0001 0514 4044. GRID: grid.411680.a FAU - Zhang, Liang AU - Zhang L AD - 1Department of Physiology, Medical College of Shihezi University, 59 North 2nd Road, Shihezi, Xinjiang 832002 People's Republic of China. ISNI: 0000 0001 0514 4044. GRID: grid.411680.a AD - 2Key Laboratory of Xingjiang Endemic and Ethnic Diseases, Medical College of Shihezi University, Shihezi, Xinjiang China. ISNI: 0000 0001 0514 4044. GRID: grid.411680.a FAU - Li, Li AU - Li L AD - 1Department of Physiology, Medical College of Shihezi University, 59 North 2nd Road, Shihezi, Xinjiang 832002 People's Republic of China. ISNI: 0000 0001 0514 4044. GRID: grid.411680.a AD - 2Key Laboratory of Xingjiang Endemic and Ethnic Diseases, Medical College of Shihezi University, Shihezi, Xinjiang China. ISNI: 0000 0001 0514 4044. GRID: grid.411680.a FAU - Si, Jun-Qiang AU - Si JQ AD - 1Department of Physiology, Medical College of Shihezi University, 59 North 2nd Road, Shihezi, Xinjiang 832002 People's Republic of China. ISNI: 0000 0001 0514 4044. GRID: grid.411680.a AD - 2Key Laboratory of Xingjiang Endemic and Ethnic Diseases, Medical College of Shihezi University, Shihezi, Xinjiang China. ISNI: 0000 0001 0514 4044. GRID: grid.411680.a FAU - Ma, Ke-Tao AU - Ma KT AUID- ORCID: 0000-0001-5220-7239 AD - 1Department of Physiology, Medical College of Shihezi University, 59 North 2nd Road, Shihezi, Xinjiang 832002 People's Republic of China. ISNI: 0000 0001 0514 4044. GRID: grid.411680.a AD - 2Key Laboratory of Xingjiang Endemic and Ethnic Diseases, Medical College of Shihezi University, Shihezi, Xinjiang China. ISNI: 0000 0001 0514 4044. GRID: grid.411680.a LA - eng PT - Journal Article DEP - 20180820 PL - England TA - Cell Mol Biol Lett JT - Cellular & molecular biology letters JID - 9607427 RN - 0 (Connexin 43) RN - 0 (Connexins) RN - 0 (Interleukins) SB - IM MH - Animals MH - CD4-CD8 Ratio MH - Connexin 43/analysis/immunology MH - Connexins/analysis/immunology MH - Gap Junctions/immunology/*pathology MH - Hypertension/blood/*complications/immunology/*pathology MH - Inflammation/blood/*etiology/immunology/*pathology MH - Interleukins/blood/immunology MH - Lymphocytes/immunology/*pathology MH - Male MH - Rats, Inbred SHR MH - Rats, Inbred WKY MH - Gap Junction alpha-5 Protein PMC - PMC6102908 OTO - NOTNLM OT - Connexins OT - Hypertension-mediated inflammation OT - Spontaneously hypertensive rats OT - T lymphocytes COIS- Xin-zhi Li is from the Department of Pathophysiology of the Medical College of Shihezi University. The other authors are from the Department of Physiology of the Medical College of Shihezi University.This manuscript does not report on studies involving human participants, human data or human tissue. The protocol of the study was approved by Institutional Animal Care and Use Committees (IACUC) of the Medical College of Shihezi University, and all animal handling and experimental procedures were performed in accordance with guidelines for the Care and Use of Laboratory Animals published by the US National Institutes of Health (Public Health Service Policy on Humane Care and Use of Animals, DHEW Publication No. 96-01, PHS Policy revised in 2002).Not applicableThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/08/29 06:00 MHDA- 2018/10/30 06:00 PMCR- 2018/08/20 CRDT- 2018/08/29 06:00 PHST- 2018/01/15 00:00 [received] PHST- 2018/08/06 00:00 [accepted] PHST- 2018/08/29 06:00 [entrez] PHST- 2018/08/29 06:00 [pubmed] PHST- 2018/10/30 06:00 [medline] PHST- 2018/08/20 00:00 [pmc-release] AID - 106 [pii] AID - 10.1186/s11658-018-0106-0 [doi] PST - epublish SO - Cell Mol Biol Lett. 2018 Aug 20;23:40. doi: 10.1186/s11658-018-0106-0. eCollection 2018.