Next Article in Journal
A High Redox Potential Laccase from Pycnoporus sanguineus RP15: Potential Application for Dye Decolorization
Previous Article in Journal
Supercritical Carbon Dioxide and Microwave-Assisted Extraction of Functional Lipophilic Compounds from Arthrospira platensis
Article Menu
Issue 5 (May) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2016, 17(5), 674; doi:10.3390/ijms17050674

Guanabenz Downregulates Inflammatory Responses via eIF2α Dependent and Independent Signaling

Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA
Department of Orthopadic Surgery, Mie University Graduate School of Medicine, Mie 514-8507, Japan
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 40907, USA
Department of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin 150081, China
Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, 1–100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Japan
Author to whom correspondence should be addressed.
Academic Editor: Charles J. Malemud
Received: 26 March 2016 / Revised: 22 April 2016 / Accepted: 27 April 2016 / Published: 5 May 2016
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [2737 KB, uploaded 5 May 2016]   |  


Integrated stress responses (ISR) may lead to cell death and tissue degeneration via eukaryotic translation initiation factor 2 α (eIF2α)-mediated signaling. Alleviating ISR by modulating eIF2α phosphorylation can reduce the symptoms associated with various diseases. Guanabenz is known to elevate the phosphorylation level of eIF2α and reduce pro-inflammatory responses. However, the mechanism of its action is not well understood. In this study, we investigated the signaling pathway through which guanabenz induces anti-inflammatory effects in immune cells, in particular macrophages. Genome-wide mRNA profiling followed by principal component analysis predicted that colony stimulating factor 2 (Csf2, or GM-CSF as granulocyte macrophage colony stimulating factor) is involved in the responses to guanabenz. A partial silencing of Csf2 or eIF2α by RNA interference revealed that Interleukin-6 (IL6), Csf2, and Cyclooxygenase-2 (Cox2) are downregulated by guanabenz-driven phosphorylation of eIF2α. Although expression of IL1β and Tumor Necrosis Factor-α (TNFα) was suppressed by guanabenz, their downregulation was not directly mediated by eIF2α signaling. Collectively, the result herein indicates that anti-inflammatory effects by guanabenz are mediated by not only eIF2α-dependent but also eIF2α-independent signaling. View Full-Text
Keywords: guanabenz; microarray; inflammation; Csf2 (GM-CSF); eIF2α signaling guanabenz; microarray; inflammation; Csf2 (GM-CSF); eIF2α signaling

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Takigawa, S.; Chen, A.; Nishimura, A.; Liu, S.; Li, B.-Y.; Sudo, A.; Yokota, H.; Hamamura, K. Guanabenz Downregulates Inflammatory Responses via eIF2α Dependent and Independent Signaling. Int. J. Mol. Sci. 2016, 17, 674.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top