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Dual modulation of formyl peptide receptor 2 by aspirin-triggered lipoxin contributes to its anti-inflammatory activity
- Source :
- FASEB journal : official publication of the Federation of American Societies for Experimental BiologyREFERENCES. 34(5)
- Publication Year :
- 2019
-
Abstract
- The eicosanoid lipoxin A4 and aspirin-triggered 15-epi-lipoxin A4 (ATL) are potent anti-inflammatory agents. How their anti-inflammatory effects are mediated by receptors such as the formyl peptide receptor 2 (FPR2/ALX) remains incompletely understood. In the present study, fluorescent biosensors of FPR2/ALX were prepared and ATL-induced conformational changes were recorded. A biphasic dose curve consisting of a descending phase and an ascending phase was observed, with the descending phase corresponding to diminished FPR2 response such as Ca2+ mobilization induced by the potent synthetic agonist WKYMVm. Preincubation of FPR2-expressing cells with 100 pM of ATL also lowered the threshold for WKYMVm to induce β-arrestin-2 membrane translocation, and inhibited WKYMVm-induced interleukin 8 secretion, suggesting signaling bias favoring anti-inflammatory activities. At 100 pM and above, ATL-induced receptor conformational changes resembling that of the WKYMVm along with a weak but measurable inhibition of forskolin-induced cAMP accumulation. However, no Ca2+ mobilization was induced by ATL until its concentration reached 1 µM. Taken together, these results suggest a dual regulatory mechanism by which ATL exerts anti-inflammatory effects through FPR2/ALX.
- Subjects :
- 0301 basic medicine
Agonist
Models, Molecular
Interleukin-8 secretion
medicine.drug_class
Protein Conformation
Inflammation
HL-60 Cells
Biosensing Techniques
Pharmacology
Biochemistry
Formyl peptide receptor 2
Cell Line
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Genetics
medicine
Animals
Humans
Calcium Signaling
Receptors, Lipoxin
Receptor
Molecular Biology
G protein-coupled receptor
Fluorescent Dyes
Lipoxin
Aspirin
Chemistry
Anti-Inflammatory Agents, Non-Steroidal
Interleukin-8
Receptors, Formyl Peptide
Rats
Lipoxins
030104 developmental biology
HEK293 Cells
Eicosanoid
medicine.symptom
Oligopeptides
030217 neurology & neurosurgery
Biotechnology
Signal Transduction
Subjects
Details
- ISSN :
- 15306860
- Volume :
- 34
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- FASEB journal : official publication of the Federation of American Societies for Experimental BiologyREFERENCES
- Accession number :
- edsair.doi.dedup.....d5b40fd7df9ff2184472eff74ce30eb8