Phospholipase A1 Member A Activates Fibroblast-like Synoviocytes through the Autotaxin-Lysophosphatidic Acid Receptor Axis.

Yang Zhao,John Di Battista,Eric Boilard,Chenqi Zhao,Lynn Davis,Myriam Vaillancourt,Patrice E Poubelle,Paul Fortin,Sylvain G Bourgoin,Stephan Hasse

doi:10.3390/ijms222312685

Abstract

Lysophosphatidylserine (lysoPS) is known to regulate immune cell functions. Phospholipase A1 member A (PLA1A) can generate this bioactive lipid through hydrolysis of sn-1 fatty acids on phosphatidylserine (PS). PLA1A has been associated with cancer metastasis, asthma, as well as acute coronary syndrome. However, the functions of PLA1A in the development of systemic autoimmune rheumatic diseases remain elusive. To investigate the possible implication of PLA1A during rheumatic diseases, we monitored PLA1A in synovial fluids from patients with rheumatoid arthritis and plasma of early-diagnosed arthritis (EA) patients and clinically stable systemic lupus erythematosus (SLE) patients. We used human primary fibroblast-like synoviocytes (FLSs) to evaluate the PLA1A-induced biological responses. Our results highlighted that the plasma concentrations of PLA1A in EA and SLE patients were elevated compared to healthy donors. High concentrations of PLA1A were also detected in synovial fluids from rheumatoid arthritis patients compared to those from osteoarthritis (OA) and gout patients. The origin of PLA1A in FLSs and the arthritic joints remained unknown, as healthy human primary FLSs does not express the PLA1A transcript. Besides, the addition of recombinant PLA1A stimulated cultured human primary FLSs to secrete IL-8. Preincubation with heparin, autotaxin (ATX) inhibitor HA130 or lysophosphatidic acid (LPA) receptor antagonist Ki16425 reduced PLA1A-induced-secretion of IL-8. Our data suggested that FLS-associated PLA1A cleaves membrane-exposed PS into lysoPS, which is subsequently converted to LPA by ATX. Since primary FLSs do not express any lysoPS receptors, the data suggested PLA1A-mediated pro-inflammatory responses through the ATX-LPA receptor signaling axis.

Highlights

Phospholipase A1 member A (PLA1A, known as PS-phospholipase A1 (PLA1)) belongs to the pancreatic lipase family and was purified initially from the thrombin-activated platelet-rich plasma of rats [1]
We demonstrate that the pro-inflammatory effects of PLA1A in fibroblast-like synoviocytes (FLSs) were, at least in part, dependent on the ATX-lysophosphatidic acid (LPA) receptor axis
We first examined by ELISA the concentrations of PLA1A in platelet-free plasma from 12 healthy donors, 38 early-diagnosed arthritis (EA) patients, and 62 systemic lupus erythematosus (SLE) patients u2n.dReregsouinltgs treatment as well as in hyaluronidase-treated synovial fluids from five rheumatoid arthritis (RA)

Summary

Introduction

Phospholipase A1 member A (PLA1A, known as PS-PLA1) belongs to the pancreatic lipase family and was purified initially from the thrombin-activated platelet-rich plasma of rats [1]. High PLA1A expression was reported in the airway epithelium in asthma [4], in vascular endothelial cells of heart transplant rejection [5], as well as in non-metastasis melanoma cell lines [6] and prostate cancer tissues [7]. In this regard, the expression of PLA1A is restricted to inflammatory disorders [8] and associated with oncogenesis and cancer metastasis [9]. The production of lysoPS, which has immune-suppressive properties [14], may at least in part explain the biological functions of PLA1A

Methods

Results

Discussion

Conclusion