Format

Send to

Choose Destination
Prostaglandins Other Lipid Mediat. 2019 Aug;143:106340. doi: 10.1016/j.prostaglandins.2019.106340. Epub 2019 May 23.

Respective contribution of cytosolic phospholipase A2α and secreted phospholipase A2 IIA to inflammation and eicosanoid production in arthritis.

Author information

1
Centre de Recherche du Centre Hospitalier Universitaire de Québec, Faculté de Médecine de l'Université Laval, Département de microbiologie et immunologie, Québec, QC, G1V 4G2, Canada.
2
Centre de Recherche du Centre Hospitalier Universitaire de Québec, Faculté de Médecine de l'Université Laval, Département de microbiologie et immunologie, Québec, QC, G1V 4G2, Canada; Department of Chemistry and Biochemistry, Université de Moncton, Moncton, E1A 3E9, Canada.
3
Department of Chemistry, University of Washington, Seattle, WA, 98195, USA.
4
Centre de Recherche du Centre Hospitalier Universitaire de Québec, Faculté de Médecine de l'Université Laval, Département de microbiologie et immunologie, Québec, QC, G1V 4G2, Canada; Canadian National Transplantation Research Program, Edmonton, Alberta, Canada. Electronic address: eric.boilard@crchudequebec.ulaval.ca.

Abstract

Phospholipase A2s (PLA2) play a key role in generation of eicosanoids. Cytosolic PLA2α (cPLA2α) is constitutively expressed in most cells, whereas IIA secreted PLA2 (sPLA2-IIA) is induced during inflammation and is present at high levels in the synovial fluid of rheumatoid arthritis patients. In mice, both cPLA2α and sPLA2-IIA have been implicated in autoimmune arthritis; however, the respective contribution of these two enzymes to the pathogenesis and production of eicosanoids is unknown. We evaluated the respective role of cPLA2α and sPLA2-IIA with regard to arthritis and eicosanoid profile in an in vivo model of arthritis. While arthritis was most severe in mice expressing both enzymes, it was abolished when both cPLA2α and sPLA2-IIA were lacking. cPLA2α played a dominant role in the severity of arthritis, although sPLA2-IIA sufficed to significantly contribute to the disease. Several eicosanoids were modulated during the course of arthritis and numerous species involved sPLA2-IIA expression. This study confirms the critical role of PLA2s in arthritis and unveils the distinct contribution of cPLA2α and sPLA2-IIA to the eicosanoid profile in arthritis.

KEYWORDS:

Arthritis; Eicosanoids; Mice; Phospholipase A2

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center