Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Teppan, J; Schwanzer, J; Rittchen, S; Bärnthaler, T; Lindemann, J; Nayak, B; Reiter, B; Luschnig, P; Farzi, A; Heinemann, A; Sturm, E.
The disrupted molecular circadian clock of monocytes and macrophages in allergic inflammation.
Front Immunol. 2024; 15: 1408772
Doi: 10.3389/fimmu.2024.1408772
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- Führende Autor*innen der Med Uni Graz
- Böhm Eva
- Teppan Julia
- Co-Autor*innen der Med Uni Graz
- Bärnthaler Thomas
- Farzi Aitak
- Heinemann Akos
- Lindenmann Jörg
- Luschnig Petra
- Nayak Barsha Baisakhi
- Reiter Bernhard
- Rittchen Sonja
- Schwanzer Juliana
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- Abstract:
- INTRODUCTION: Macrophage dysfunction is a common feature of inflammatory disorders such as asthma, which is characterized by a strong circadian rhythm. METHODS AND RESULTS: We monitored the protein expression pattern of the molecular circadian clock in human peripheral blood monocytes from healthy, allergic, and asthmatic donors during a whole day. Monocytes cultured of these donors allowed us to examine circadian protein expression in human monocyte-derived macrophages, M1- and M2- polarized macrophages. In monocytes, particularly from allergic asthmatics, the oscillating expression of circadian proteins CLOCK, BMAL, REV ERBs, and RORs was significantly altered. Similar changes in BMAL1 were observed in polarized macrophages from allergic donors and in tissue-resident macrophages from activated precision cut lung slices. We confirmed clock modulating, anti-inflammatory, and lung-protective properties of the inverse ROR agonist SR1001 by reduced secretion of macrophage inflammatory protein and increase in phagocytosis. Using a house dust mite model, we verified the therapeutic effect of SR1001 in vivo. DISCUSSION: Overall, our data suggest an interaction between the molecular circadian clock and monocytes/macrophages effector function in inflammatory lung diseases. The use of SR1001 leads to inflammatory resolution in vitro and in vivo and represents a promising clock-based therapeutic approach for chronic pulmonary diseases such as asthma.
- Find related publications in this database (using NLM MeSH Indexing)
- Humans - administration & dosage
- Monocytes - immunology, metabolism
- Circadian Clocks - immunology
- Animals - administration & dosage
- Macrophages - immunology, metabolism
- Asthma - immunology, metabolism
- Male - administration & dosage
- Hypersensitivity - immunology, metabolism
- Inflammation - immunology
- Female - administration & dosage
- Mice - administration & dosage
- Adult - administration & dosage
- Pyroglyphidae - immunology
- Cells, Cultured - administration & dosage
- Circadian Rhythm - immunology
- Find related publications in this database (Keywords)
- molecular circadian clock
- macrophages
- inflammation
- circadian proteins
- REV ERB agonist SR9009
- inverse ROR agonist SR1001