Inhibition of antigen-induced arthritis in guinea pigs by a selective LTB4 receptor antagonist LY293111Na

Kuwabara, Kenji; Jyoyama, Hirokuni; Fleisch, Jerome H.; Hori, Yozo

doi:10.1007/pl00012425

Cited by 11 publications

(8 citation statements)

References 40 publications

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“…MPO is a specific enzyme of polymorphonuclear leucocytes (PMN) and is released when these cells are stimulated during inflammatory reactions. Increased MPO activity was observed in antigen-induced arthritis in guinea pigs and was attributed to neutrophils attracted to synovial tissue (Kuwabara et al, 2002). It has recently been reported that MPO mRNA levels are increased in osteoarthritic chondrocytes (Attur et al, 2002).…”

Section: Discussionmentioning

confidence: 98%

A type II-collagen derived peptide and its nitrated form as new markers of inflammation and cartilage degradation in equine osteochondral lesions

Gangl

Serteyn

Lejeune³

et al. 2007

Research in Veterinary Science

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Markers of cartilage breakdown enable studying the degradation of cartilage matrix in equine joint pathologies. This study was designed to determine the levels of Coll2-1, a peptide of the triple helix of type II collagen, and Coll2-1NO 2 , its nitrated form in the plasma of healthy horses (controls; n = 37) and horses suffering from osteochondrosis (n = 34). Clinical and arthroscopic scores were attributed reflecting the severity of lesions and were related to the plasma levels of Coll2-1 and Coll2-1NO 2 . The median of Coll2-1 was significantly higher in the control group, whereas the mean of Coll2-1NO 2 showed significant elevation in the pathological group. However, the measurement means of scoring classes did not vary significantly. The markers were able to differentiate the group of horses suffering from osteochondrosis from the group of healthy horses. The elevation of Coll2-1NO 2 in the pathological group indicates an inflammation, mediated through reactive oxygen species and/or increased myeloperoxidase activity.

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Section: Discussionmentioning

confidence: 98%

A type II-collagen derived peptide and its nitrated form as new markers of inflammation and cartilage degradation in equine osteochondral lesions

Gangl

Serteyn

Lejeune³

et al. 2007

Research in Veterinary Science

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“…This demonstrates that guinea pigs might be a useful animal model in preclinical tests of MPGES1 inhibitors. In addition, guinea pigs have been used to study inflammatory diseases in several models of arthritis, including antigen-induced arthritis (18) and adjuvant-induced arthritis (19, 20). Although guinea pigs and humans share the same amino acid residues in positions 131, 135, and 138 of MPGES1, allowing for species discriminating MPGES1 inhibitors to bind, the overall identity of the two enzymes is only 79%.…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Residues Determining Species Differences in Inhibitor Binding of Microsomal Prostaglandin E Synthase-1*

Pawelzik

Uda

Spahiu³

et al. 2010

Journal of Biological Chemistry

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Microsomal prostaglandin E synthase-1 (MPGES1) is induced during an inflammatory reaction from low basal levels by pro-inflammatory cytokines and subsequently involved in the production of the important mediator of inflammation, prostaglandin E2. Nonsteroidal anti-inflammatory drugs prevent prostaglandin E2 production by inhibiting the upstream enzymes cyclooxygenases 1 and 2. In contrast to these conventional drugs, a new generation of NSAIDs targets the terminal enzyme MPGES1. Some of these compounds potently inhibit human MPGES1 but do not have an effect on the rat orthologue. We investigated this interspecies difference in a rat/human chimeric form of the enzyme as well as in several mutants and identified key residues Thr-131, Leu-135, and Ala-138 in human MPGES1, which play a crucial role as gate keepers for the active site of MPGES1. These residues are situated in transmembrane helix 4, lining the entrance to the cleft between two subunits in the protein trimer, and regulate access of the inhibitor in the rat enzyme. Exchange toward the human residues in rat MPGES1 was accompanied with a gain of inhibitor activity, whereas exchange in human MPGES1 toward the residues found in rat abrogated inhibitor activity. Our data give evidence for the location of the active site at the interface between subunits in the homotrimeric enzyme and suggest a model of how the natural substrate PGH2, or competitive inhibitors of MPGES1, enter the active site via the phospholipid bilayer of the membrane.

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“…In human medicine, MPO has been measured as a marker of neutrophil activation and tissue infiltration in a broad variety of pathologies (Serteyn et al 2003), including OA (Deberg et al 2008). Increased MPO activity was also observed in antigen-induced arthritis in guinea pigs and was attributed to neutrophils that were attracted to synovial tissue (Kuwabara et al 2002).…”

Section: Introductionmentioning

confidence: 97%

Coll2-1, Coll2-1NO2 and myeloperoxidase concentrations in the synovial fluid of equine tarsocrural joints affected with osteochondrosis

et al. 2011

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The measurement of biomarkers that reflect cartilage breakdown is a powerful tool for investigating joint damage caused by disease or injury. Particularly in cases of osteochondrosis, synovial concentrations of these biomarkers may reveal the presence of osteoarthritic changes. Coll2-1, Coll2-1 NO2 and myeloperoxidase have recently been introduced in equine osteoarticular research but comparison between the concentrations of these markers in OCD affected and healthy joints has not been made. Therefore, this study aimed at reporting the synovial concentrations of these biomarkers in joints affected with osteochondral fragments in the tarsocrural joint compared to unaffected joints. Myeloperoxidase and Coll2-1NO2 revealed to have similar levels between affected joints and controls. However, in contrast to previous studies using C2C the present study demonstrated that synovial levels of Coll2-1 were significantly elevated in tarsocrural joints affected with osteochondrosis. Thus, Coll2-1 may be an earlier marker of cartilage degeneration than other cartilage degradation markers that have been previously used in equine medicine.

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Inhibition of antigen-induced arthritis in guinea pigs by a selective LTB4 receptor antagonist LY293111Na

Cited by 11 publications

References 40 publications

A type II-collagen derived peptide and its nitrated form as new markers of inflammation and cartilage degradation in equine osteochondral lesions

A type II-collagen derived peptide and its nitrated form as new markers of inflammation and cartilage degradation in equine osteochondral lesions

Identification of Key Residues Determining Species Differences in Inhibitor Binding of Microsomal Prostaglandin E Synthase-1*

Coll2-1, Coll2-1NO2 and myeloperoxidase concentrations in the synovial fluid of equine tarsocrural joints affected with osteochondrosis

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