International Journal of Medical Sciences

Impact factor
2.399

22 October 2017

ISSN 1449-1907 News feeds of published articles

My Manuscript | My Account

Journal of Genomics now in PubMed/PubMed Central. Submit manuscript...

Journal of Biomedicinenew

Theranostics

Journal of Cancer

Oncomedicine

International Journal of Biological Sciences

Journal of Genomics

Journal of Bone and Joint Infection (JBJI)

Nanotheranostics

PubMed Central Indexed in Journal Impact Factor

Int J Med Sci 2017; 14(12):1268-1275. doi:10.7150/ijms.21573

Research Paper

Chlorpheniramine attenuates histamine-mediated aquaporin 5 downregulation in human nasal epithelial cells via suppression of NF-κB activation

Yung-Lung Chang1, Chun-Shu Lin2, Hsing-Won Wang3,4, Kai Ren Jian1, Shao-Cheng Liu3✉

1. Department of Biochemistry, National Defense Medical Center
2. Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center
3. Department of Otolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center
4. Department of Otolaryngology-Head and Neck Surgery, Shuang Ho Hospital Taipei, Taiwan, Republic of China

Abstract

Background: Aquaporin 5 (AQP5) is most likely the primary water channel in the human nasal mucosa and acts as a key tight junction protein. The signaling cascades responsible for AQP5 regulation are still works in progress.

Objective: This study sought to determine the effects of histamine and chlorpheniramine on AQP5 expression in human nasal epithelial cells (HNEpC) and to detect the signaling cascades responsible for these effects.

Methods: HNEpC were cultured with four concentrations of histamine or chlorpheniramine in vitro. The sub-cellular distribution of AQP5 was explored using immunocytochemistry. The pharmacologic effects of histamine and chlorpheniramine on the expression of the phosphorylation of cyclic adenosine monophosphate-responsive element binding protein (p-CREB), the AQP5 and the NF-κB protein were examined using Western blotting.

Results: AQP5 was found to be located in cell membrane and cytoplasm and present in every group without significant difference. Histamine inhibits the expression of AQP5 and p-CREB in HNEpC, while chlorpheniramine dose-dependently increases these protein levels with statistical significance. HNEpC treated with histamine and chlorpheniramine in turn showed the same trends as those intervened separately with these two drugs. Moreover, chlorpheniramine had the ability to reverse the inhibitory effect of histamine. Western blotting analysis revealed that after incubation with 10-4 M histamine, NF-κB protein was significantly heightened by 165% compared with the untreated control group. Again, such increase can be significantly reversed after chlorpheniramine treatment.

Conclusions: The current study demonstrated that histamine inhibits CREB phosphorylation in HNEpC, which results in decreased AQP5 expression via activation of NF-κB pathway. Chlorpheniramine attenuates the inhibitory effect of histamine in p-CREB/AQP5 expression via suppression of NF-κB signal cascades. This observation could provide additional insight into the anti-inflammatory effects of H1-antihistamines that contribute to maintain airway surface liquid and mucosal defense.

Keywords: AQP5, cAMP, CREB, antihistamine, NF-κB, nasal mucosa, histamine

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Chang YL, Lin CS, Wang HW, Jian KR, Liu SC. Chlorpheniramine attenuates histamine-mediated aquaporin 5 downregulation in human nasal epithelial cells via suppression of NF-κB activation. Int J Med Sci 2017; 14(12):1268-1275. doi:10.7150/ijms.21573. Available from http://www.medsci.org/v14p1268.htm