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Dual modulation of formyl peptide receptor 2 by aspirin-triggered lipoxin contributes to its anti-inflammatory activity
Ge,Yunjun1; Zhang,Shuo2; Wang,Junlin1; Xia,Fangbo1; Wan,Jian Bo1; Lu,Jinjian1; Ye,Richard D.1,3
2020-05-01
Source PublicationFASEB Journal
ISSN0892-6638
Volume34Issue:5Pages:6920-6933
Abstract

The eicosanoid lipoxin A and aspirin-triggered 15-epi-lipoxin A (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 Ca 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 Ca 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.

KeywordBiased Signaling g Protein-coupled Receptor Inflammation Inverse Agonism
DOI10.1096/fj.201903206R
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaBiochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics ; Cell Biology
WOS SubjectBiochemistry & Molecular Biology ; Biology ; Cell Biology
WOS IDWOS:000522968700001
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Cited Times [WOS]:11   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorYe,Richard D.
Affiliation1.State Key Laboratory for Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macau,Macao
2.School of Pharmacy,Shanghai Jiao Tong University,Shanghai,China
3.Kobilka Institute of Innovative Drug Discovery,School of Life and Health Sciences,The Chinese University of Hong Kong,Shenzhen,China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Ge,Yunjun,Zhang,Shuo,Wang,Junlin,et al. Dual modulation of formyl peptide receptor 2 by aspirin-triggered lipoxin contributes to its anti-inflammatory activity[J]. FASEB Journal,2020,34(5):6920-6933.
APA Ge,Yunjun,Zhang,Shuo,Wang,Junlin,Xia,Fangbo,Wan,Jian Bo,Lu,Jinjian,&Ye,Richard D..(2020).Dual modulation of formyl peptide receptor 2 by aspirin-triggered lipoxin contributes to its anti-inflammatory activity.FASEB Journal,34(5),6920-6933.
MLA Ge,Yunjun,et al."Dual modulation of formyl peptide receptor 2 by aspirin-triggered lipoxin contributes to its anti-inflammatory activity".FASEB Journal 34.5(2020):6920-6933.
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