Expression of 5-lipoxygenase and 15-lipoxygenase in rheumatoid arthritis synovium and effects of intraarticular glucocorticoids.
BACKGROUND
It was previously shown that lipoxygenase (LO) pathways are important in the rheumatoid arthritis (RA) inflammatory process and that synovial fluid from RA patients contains high amounts of leukotrienes. We therefore aimed to investigate the 5-LO and 15-LO-1 expression pattern in RA and ostheoarthritis (OA) synovial tissue and to study the effect of intraarticular glucocorticoid (GC) therapy on enzyme expression.


METHODS
Expression of LOs was evaluated by immunohistochemistry in RA and OA synovial biopsies. Cellular localization of these enzymes was analyzed by double immunofluorescence. In synovial biopsies from 11 RA patients, 5-LO and 15-LO-1 expression was evaluated before and after triamcinolone hexacetonide knee injection and assessed by image analysis to quantify their expression. We also investigated the presence of 15-LO-1 by immunohistochemistry in synovial fluid (SF) cells as well as their ability to form 15-hydroxyeicosatetraenoic acid (15-HETE) following treatment with arachidonic acid (AA).


RESULTS
5-LO and 15-LO-1 are present in RA and OA synovium, with 5-LO being mostly expressed in lining and sublining macrophages, neutrophils and mast cells and 15-LO-1 mainly in lining macrophages, fibroblasts and sublining endothelial cells. Intraarticular GC treatment resulted in a significant suppression of 5-LO expression, but did not influence the 15-LO-1 enzyme significantly. Also, SF cells express a functional 15-LO-1 and produce 15-HETE when challenged with AA.


CONCLUSIONS
These data demonstrate that local therapy with GC decreases 5-LO expression in RA synovium and offer an additional possible mechanism for the efficiency of intraarticular adjuvant therapy in RA.
Gheorghe
Karina Roxana
KR
Department of Biosciences and Nutrition, Novum, Karolinska Institute, SE-141 57 Huddinge, Sweden. karina.gheorghe@ki.se
Korotkova
Marina
M
Catrina
Anca Irinel
AI
Backman
Linda
L
af Klint
Erik
E
Claesson
Hans-Erik
HE
Rådmark
Olof
O
Jakobsson
Per-Johan
PJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001093:Arachidonate 15-Lipoxygenase / Q000096:biosynthesis* / Q000235:genetics; D001094:Arachidonate 5-Lipoxygenase / Q000096:biosynthesis* / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007270:Injections, Intra-Articular; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013583:Synovial Membrane / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology
D005938:Glucocorticoids; D001093:Arachidonate 15-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase