Differential production of leukotriene B4 or prostaglandin E2 by WKYMVm or serum amyloid A via formyl peptide receptor-like 1.
Serum amyloid A (SAA) and Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm) have been reported as formyl peptide receptor-like 1 (FPRL1) ligands. WKYMVm but not SAA stimulated superoxide generation by human neutrophils. In terms of the downstream signalings triggered by WKYMVm and SAA, both agonists stimulated cytosolic phospholipase A2-mediated arachidonic acid release, a precursor of leukotriene B4 (LTB4) and prostaglandin E2 (PGE2). WKYMVm also strongly stimulated LTB4 production in human neutrophils without affecting PGE2 production, whereas SAA strongly stimulates cyclooxygenase-2 (COX-2) expression and PGE2 production but not LTB4 production. In terms of the receptors responsible for the differential actions of these two agonists, we found that FPRL1 is involved in the production of LTB4 by WKYMVm and PGE2 production by SAA. This study demonstrates that the chemoattractant receptor, FPRL1, can be differentially regulated by distinct ligands to generate different lipid mediators, and thus, different immune responses.
Lee
Ha Young
HY
Medical Research Center for Cancer Molecular Therapy, Dong-A University, Busan, Republic of Korea.
Jo
Seong Ho
SH
Lee
Chuhee
C
Baek
Suk-Hwan
SH
Bae
Yoe-Sik
YS
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D045744:Cell Line, Tumor; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004586:Electrophoresis / Q000379:methods; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D007975:Leukotriene B4 / Q000096:biosynthesis*; D050356:Lipid Metabolism / Q000187:drug effects; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D044042:Receptors, Formyl Peptide / Q000378:metabolism*; D000685:Serum Amyloid A Protein / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors
C469986:FPR1 protein, human; D009842:Oligopeptides; D044042:Receptors, Formyl Peptide; D000685:Serum Amyloid A Protein; C113617:Trp-Lys-Tyr-Met-Val-Met; D013481:Superoxides; D007975:Leukotriene B4; D016718:Arachidonic Acid; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone