Interleukin‐1 activates phospholipase a<sub>2</sub> IN HUMAN SYNOVIAL CELLS

Gilman, Steven C.; Chang, Joseph; Zeigler, Pamela R.; Uhl, Joanne; Mochan, Eugene

doi:10.1002/art.1780310118

Cited by 92 publications

(37 citation statements)

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“…We found a statistically significant rise in the activity of PLA, in joint fluids from valgus-operated knee joints at 7 months, but not at 18 months after operation. PLA, originates from the synovial lining cells, inflammatory cells or chondrocytes (Gilman et al 1988, Gonzales-Buritica et al 1989, Pruzanski et al 1990). Increased mechanical stimulation as a signal for initiation of PLA, production by the chondrocytes has been suggested by Chrisman and co-workers (1981).…”

Section: Discussionmentioning

confidence: 99%

Elevated levels of synovial fluid PLA₂, strome-lysin (MMP-3) and TIMP in early osteoarthrosis after tibial valgus osteotomy in young beagle dogs

Panula

Lohmander

Rönkkö³

et al. 1998

Acta Orthopaedica Scandinavica

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Section: Discussionmentioning

confidence: 99%

Elevated levels of synovial fluid PLA₂, strome-lysin (MMP-3) and TIMP in early osteoarthrosis after tibial valgus osteotomy in young beagle dogs

Panula

Lohmander

Rönkkö³

et al. 1998

Acta Orthopaedica Scandinavica

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“…Interleukin-1 and tumor necrosis factor-a have been reported to increase the expression and activity of secretory phospholipase A, in human synovial cells [23], human hepatoma cells [14], and cells from different species 124-261. However, in all of these studies activation was performed by stimulating cells with cytokines especially interleukin-lp, interleukin-6 and tumor necrosis factor-a.…”

Section: Discussionmentioning

confidence: 99%

Induction of cytosolic phospholipase A₂ in human leukocytes by lipopolysaccharide

Rodewald

Tibes

Maass

et al. 1994

European Journal of Biochemistry

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Stimulation of peripheral blood leukocytes with lipopolysaccharide results in the synthesis of inflammatory cytokines including interleukin-1/3, interleukin-6, tumor necrosis factor-a and prostaglandin E, correlating with an increase in phospholipase A, activity. Mammalian cells contain several phospholipase A, isoforms including the 14-kDa secretory isoform and the more recently described high-molecular-mass cytosolic isoform. It is commonly believed that during inflammatory responses secretory phospholipase A, becomes activated. However, we could not detect secretory phospholipase A, nor its corresponding mRNA after lipopolysaccharide-induced activation. By contrast, we found increased mRNA levels for cytosolic phospholipase A, following activation of peripheral blood leukocytes when levels were compared to non-stimulated controls. Our results demonstrate that cytosolic phospholipase A,, rather than the secretory isoform may be the mediator of the lipopolysaccharide-induced inflammatory cascade in human peripheral blood leukocytes.Phospholipase A, is a lipolytic enzyme that hydrolyzes the fatty acyl ester at the sn-2 position of glycerophosphatides producing equimolar amounts of free fatty acids and lysophosphatides. The observation that arachidonic acid (A,Ach) is predominantly found esterified at the sn-2 position suggests that the action of this enzyme is the rate-limiting step in the synthesis of leukotrienes and prostaglandins. Furthermore, phospholipase A, is involved in the formation of platelet-activating factor [ 1, 21. These observations indicate that phospholipase A, plays a significant role in the synthesis of potent mediators of inflammation. Therefore, studies were initiated to correlate phospholipase A, levels in patients with different pathophysiological conditions. Evidence now indicates that elevated phospholipase A, levels are associated with diseases like acute pancreatitis, acute and chronic colitis, rheumatoid arthritis, allergic shock, septic shock, psoriasis and thrombotic cardiovascular diseases [3]. Experiments are therefore in progress to evaluate phospholipase A, activity and immunoreactivity as a diagnostic or prognostic marker for the above-mentioned diseases To date, the different phospholipase A, have been subdivided into two main classes, the secreted forms, including type I (pancreatic) and type I1 (secretory), and the nonsecreted forms, namely type IV (cytosolic) [7].Pharmacological research has focused primarily on secretory and cytosolic phospholipase A,, two isoforms which

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“…Enhanced levels of the cytokine, interleukin (IL)-1␤, 1 perpetuate the disease process through up-regulation of a multitude of factors leading to eicosanoid formation, matrix degradation, bone resorption, and proliferation in the joint (2)(3)(4)(5)(6). We and others have demonstrated that human rheumatoid synovial fibroblast (RSF) prostaglandin (PG) E 2 accumulation in response to IL-1␤ is a direct result of the coordinate up-regulation of 85-kDa phospholipase A 2 (PLA 2 ) and the induction of COX II (6 -8).…”

mentioning

confidence: 99%

Manipulation of Distinct NFκB Proteins Alters Interleukin-1β-induced Human Rheumatoid Synovial Fibroblast Prostaglandin E2 Formation

Roshak

Jackson

McGough

et al. 1996

Journal of Biological Chemistry

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Interleukin 1␤ (IL-1␤) up-regulates human rheumatoid synovial fibroblast (RSF) 85-kDa phospholipase A 2 (PLA 2 ) and mitogen-inducible cyclooxygenase (COX) II. Promoter regions for these genes contain a motif that closely resembles the "classic" NFB consensus site. Immunoblot analysis identified NFB1 (p50), RelA (p65), and c-Rel in RSF. Upon IL-1␤-stimulation, p65 and c-Rel but not p50 protein levels were reduced suggesting nuclear translocation. IL-1␤-induced RSF nuclear extracts contained a p65-containing complex, which bound to the classical NFB consensus motif. An NFB classical oligonucleotide decoy produced a concentration-dependent decrease in IL-1-stimulated PGE 2 production (IC 50 ‫؍‬ ϳ2 M), indicating a role of NFB. Utilization of antisense technology showed that p65 but not p50 or c-Rel mediated IL-1␤-stimulated PGE 2 formation. Treated RSF could not transcribe COX II or 85-kDa PLA 2 mRNA, which reduced their respective proteins. Interestingly, stimulated IL-8 production was not inhibited by the classical NFB decoy but was reduced by treatment with antisense to both p65 and c-Rel supporting preferential binding of c-Rel-p65 to the "alternative" IL-8 B motif. Taken together, these data provide the first direct evidence for a role of p65 in COX II and 85-kDa PLA 2 gene induction and support the IL-1 activation and participation of distinct NFB protein dimers in RSF prostanoid and IL-8 formation.Rheumatoid arthritis is an autoimmune disease characterized by chronic inflammation and hyperproliferation of the synovial lining (1). Enhanced levels of the cytokine, interleukin (IL)-1␤, 1 perpetuate the disease process through up-regulation of a multitude of factors leading to eicosanoid formation, matrix degradation, bone resorption, and proliferation in the joint (2-6). We and others have demonstrated that human rheumatoid synovial fibroblast (RSF) prostaglandin (PG) E 2 accumulation in response to IL-1␤ is a direct result of the coordinate up-regulation of 85-kDa phospholipase A 2 (PLA 2 ) and the induction of COX II (6 -8). Indeed, we reported that depletion of IL-1␤-induced 85-kDa PLA 2 to basal levels by antisense severely compromised the ability of RSF to make PGE 2 . However, the mechanism(s) by which IL-1␤ regulates 85-kDa PLA 2 and COX II gene induction in this system have not been elucidated.IL-1␤ is a potent activator of nuclear factor B (NFB) (1, 9, 10) in other cell systems, and this transcription factor in turn regulates a wide variety of inflammatory and immunoregulatory genes (10 -16). 5Ј-flanking regulatory regions for both the human 85-kDa PLA 2 and COX II genes have recently been isolated (17, 18), and sequence analysis has identified a number of possible transcription factor consensus binding motifs, including NFB. The putative NFB motif in the 85-kDa PLA 2 promoter is located at Ϫ1099 base pairs (17), whereas the NFB consensus site in the human COX II promoter is located at Ϫ233 base pairs (18).NFB is a dimeric DNA binding protein comprised of members of the NFB/Rel/dorsal family of protei...

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Interleukin‐1 activates phospholipase a₂ IN HUMAN SYNOVIAL CELLS

Cited by 92 publications

References 11 publications

Elevated levels of synovial fluid PLA₂, strome-lysin (MMP-3) and TIMP in early osteoarthrosis after tibial valgus osteotomy in young beagle dogs

Elevated levels of synovial fluid PLA₂, strome-lysin (MMP-3) and TIMP in early osteoarthrosis after tibial valgus osteotomy in young beagle dogs

Induction of cytosolic phospholipase A₂ in human leukocytes by lipopolysaccharide

Manipulation of Distinct NFκB Proteins Alters Interleukin-1β-induced Human Rheumatoid Synovial Fibroblast Prostaglandin E2 Formation

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Interleukin‐1 activates phospholipase a2 IN HUMAN SYNOVIAL CELLS

Cited by 92 publications

References 11 publications

Elevated levels of synovial fluid PLA2, strome-lysin (MMP-3) and TIMP in early osteoarthrosis after tibial valgus osteotomy in young beagle dogs

Elevated levels of synovial fluid PLA2, strome-lysin (MMP-3) and TIMP in early osteoarthrosis after tibial valgus osteotomy in young beagle dogs

Induction of cytosolic phospholipase A2 in human leukocytes by lipopolysaccharide

Manipulation of Distinct NFκB Proteins Alters Interleukin-1β-induced Human Rheumatoid Synovial Fibroblast Prostaglandin E2 Formation

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Resources

About

Interleukin‐1 activates phospholipase a₂ IN HUMAN SYNOVIAL CELLS

Elevated levels of synovial fluid PLA₂, strome-lysin (MMP-3) and TIMP in early osteoarthrosis after tibial valgus osteotomy in young beagle dogs

Elevated levels of synovial fluid PLA₂, strome-lysin (MMP-3) and TIMP in early osteoarthrosis after tibial valgus osteotomy in young beagle dogs

Induction of cytosolic phospholipase A₂ in human leukocytes by lipopolysaccharide