Next Article in Journal
3D Printing PLA/Gingival Stem Cells/ EVs Upregulate miR-2861 and -210 during Osteoangiogenesis Commitment
Next Article in Special Issue
AtCRK5 Protein Kinase Exhibits a Regulatory Role in Hypocotyl Hook Development during Skotomorphogenesis
Previous Article in Journal
Genetic Aberrations Associated with Photodynamic Therapy in Colorectal Cancer Cells
Previous Article in Special Issue
Death-Associated Protein Kinase 1 Phosphorylation in Neuronal Cell Death and Neurodegenerative Disease
Article

5-Amino-1-β-D-Ribofuranosyl-Imidazole-4-Carboxamide (AICAR) Reduces Peripheral Inflammation by Macrophage Phenotype Shift

pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(13), 3255; https://doi.org/10.3390/ijms20133255
Received: 16 May 2019 / Revised: 25 June 2019 / Accepted: 27 June 2019 / Published: 2 July 2019
(This article belongs to the Special Issue Kinase Signal Transduction 2019)
The stimulation of the AMP-activated kinase (AMPK) by 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) has been associated with antihyperalgesia and the inhibition of nociceptive signaling in the spinal cord in models of paw inflammation. The attenuated nociception comes along with a strongly reduced paw edema, indicating that peripheral antiinflammatory mechanisms contribute to antinociception. In this study, we investigated the impact of AICAR on the immune cell composition in inflamed paws, as well as the regulation of inflammatory and resolving markers in macrophages. By using fluorescence-activated cell sorting (FACS) analysis and immunofluorescence, we found a significantly increased fraction of proresolving M2 macrophages and anti-inflammatory interleukin (IL)-10 in inflamed tissue, while M1 macrophages and proinflammatory cytokines such as IL-1 were decreased by AICAR in wild type mice. In AMPKα2 knock-out mice, the M2 polarization of macrophages in the paw was missing. The results were supported by experiments in primary macrophage cultures which also showed a shift to a proresolving phenotype with decreased levels of proinflammatory mediators and increased levels of antiinflammatory mediators. However, in the cell cultures, we did not observe differences between the AMPKα2+/+ and −/− cells, thus indicating that the AICAR-induced effects are at least partially AMPK-independent. In summary, our results indicate that AICAR has potent antiinflammatory and proresolving properties in inflammation which are contributing to a reduction of inflammatory edema and antinociception. View Full-Text
Keywords: AMPK; AICAR; metformin; inflammation; macrophage; cytokines AMPK; AICAR; metformin; inflammation; macrophage; cytokines
Show Figures

Graphical abstract

MDPI and ACS Style

Martin, L.M.; Möller, M.; Weiss, U.; Russe, O.Q.; Scholich, K.; Pierre, S.; Geisslinger, G.; Niederberger, E. 5-Amino-1-β-D-Ribofuranosyl-Imidazole-4-Carboxamide (AICAR) Reduces Peripheral Inflammation by Macrophage Phenotype Shift. Int. J. Mol. Sci. 2019, 20, 3255. https://doi.org/10.3390/ijms20133255

AMA Style

Martin LM, Möller M, Weiss U, Russe OQ, Scholich K, Pierre S, Geisslinger G, Niederberger E. 5-Amino-1-β-D-Ribofuranosyl-Imidazole-4-Carboxamide (AICAR) Reduces Peripheral Inflammation by Macrophage Phenotype Shift. International Journal of Molecular Sciences. 2019; 20(13):3255. https://doi.org/10.3390/ijms20133255

Chicago/Turabian Style

Martin, Lisa M., Moritz Möller, Ulrike Weiss, Otto Q. Russe, Klaus Scholich, Sandra Pierre, Gerd Geisslinger, and Ellen Niederberger. 2019. "5-Amino-1-β-D-Ribofuranosyl-Imidazole-4-Carboxamide (AICAR) Reduces Peripheral Inflammation by Macrophage Phenotype Shift" International Journal of Molecular Sciences 20, no. 13: 3255. https://doi.org/10.3390/ijms20133255

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