Next Article in Journal
Double-Headed Cationic Lipopeptides: An Emerging Class of Antimicrobials
Next Article in Special Issue
The Impact of Acute or Chronic Alcohol Intake on the NF-κB Signaling Pathway in Alcohol-Related Liver Disease
Previous Article in Journal
Microfluidic-Based Detection of AML-Specific Biomarkers Using the Example of Promyelocyte Leukemia
Previous Article in Special Issue
The Rationale for Angiotensin Receptor Neprilysin Inhibitors in a Multi-Targeted Therapeutic Approach to COVID-19
Article

Inhibition of HDAC Enzymes Contributes to Differential Expression of Pro-Inflammatory Proteins in the TLR-4 Signaling Cascade

1
Pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Faculty of Medicine, Goethe-University Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany
2
Fraunhofer Institute for Molecular Biology and Applied Ecology, Branch Translational Medicine (IME-TMP) and Fraunhofer Cluster of Excellence for Immune mediated diseases (CIMD), Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(23), 8943; https://doi.org/10.3390/ijms21238943
Received: 9 November 2020 / Revised: 21 November 2020 / Accepted: 23 November 2020 / Published: 25 November 2020
Class I and II histone deacetylases (HDAC) are considered important regulators of immunity and inflammation. Modulation of HDAC expression and activity is associated with altered inflammatory responses but reports are controversial and the specific impact of single HDACs is not clear. We examined class I and II HDACs in TLR-4 signaling pathways in murine macrophages with a focus on IκB kinase epsilon (IKKε) which has not been investigated in this context before. Therefore, we applied the pan-HDAC inhibitors (HDACi) trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA) as well as HDAC-specific siRNA. Administration of HDACi reduced HDAC activity and decreased expression of IKKε although its acetylation was increased. Other pro-inflammatory genes (IL-1β, iNOS, TNFα) also decreased while COX-2 expression increased. HDAC 2, 3 and 4, respectively, might be involved in IKKε and iNOS downregulation with potential participation of NF-κB transcription factor inhibition. Suppression of HDAC 1–3, activation of NF-κB and RNA stabilization mechanisms might contribute to increased COX-2 expression. In conclusion, our results indicate that TSA and SAHA exert a number of histone- and HDAC-independent functions. Furthermore, the data show that different HDAC enzymes fulfill different functions in macrophages and might lead to both pro- and anti-inflammatory effects which have to be considered in therapeutic approaches. View Full-Text
Keywords: HDAC; acetylation; macrophages; inflammation HDAC; acetylation; macrophages; inflammation
Show Figures

Figure 1

MDPI and ACS Style

Weiss, U.; Möller, M.; Husseini, S.A.; Manderscheid, C.; Häusler, J.; Geisslinger, G.; Niederberger, E. Inhibition of HDAC Enzymes Contributes to Differential Expression of Pro-Inflammatory Proteins in the TLR-4 Signaling Cascade. Int. J. Mol. Sci. 2020, 21, 8943. https://doi.org/10.3390/ijms21238943

AMA Style

Weiss U, Möller M, Husseini SA, Manderscheid C, Häusler J, Geisslinger G, Niederberger E. Inhibition of HDAC Enzymes Contributes to Differential Expression of Pro-Inflammatory Proteins in the TLR-4 Signaling Cascade. International Journal of Molecular Sciences. 2020; 21(23):8943. https://doi.org/10.3390/ijms21238943

Chicago/Turabian Style

Weiss, Ulrike, Moritz Möller, Sayed A. Husseini, Christine Manderscheid, Julia Häusler, Gerd Geisslinger, and Ellen Niederberger. 2020. "Inhibition of HDAC Enzymes Contributes to Differential Expression of Pro-Inflammatory Proteins in the TLR-4 Signaling Cascade" International Journal of Molecular Sciences 21, no. 23: 8943. https://doi.org/10.3390/ijms21238943

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

Article Access Map by Country/Region

1
Back to TopTop