Antigen‐induced arthritis in mice

Brackertz, D.; Mitchell, Graham F.; Mackay, Ian R.

doi:10.1002/art.1780200314

Cited by 288 publications

(91 citation statements)

References 25 publications

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“…AIA is an experimental autoimmune arthritis and closely resembles RA histopathologically (17). Although AIA is a monoarthritis model, it has the advantage for a precise and fair histological comparison.…”

Section: Resultsmentioning

confidence: 99%

“…AIA is an immunological arthritis model (17), and IL-6 is well known as an important mediator for immunological reactions (23). To examine antigen-specific immune response in IL-6 Ϫ͞Ϫ mice after the induction of AIA, both mBSAspecific in vitro proliferative response in LNC and in vivo antibody response were measured in IL-6 Ϫ͞Ϫ mice.…”

Section: Resultsmentioning

confidence: 99%

“…Induction of AIA. AIA was induced by following the same protocol (17). Briefly, mice were immunized intradermally at the base of the tail and four footpads with 100 g of methylated BSA (mBSA) (Sigma) emulsified with an equal volume of complete Freund's adjuvant (Difco).…”

Section: Methodsmentioning

confidence: 99%

“…Antigen-induced arthritis (AIA) is an animal model for arthritis initially induced in rabbits and extended into mice (17). AIA is T cell-dependent immunological arthritis, and its histopathological features closely resemble those of RA.…”

mentioning

confidence: 99%

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Interleukin 6 plays a key role in the development of antigen-induced arthritis

Ohshima

Saeki²,

Mima³

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

364

240

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To investigate the direct role of interleukin (IL) 6 in the development of rheumatoid arthritis, IL-6-deficient (IL-6 ؊͞؊) mice were backcrossed for eight generations into C57BL͞6 mice, a strain of mice with a genetic background of susceptibility for antigen-induced arthritis (AIA). Both histological and immunological comparisons were made between IL-6-deficient (IL-6 ؊͞؊) mice and wild-type (IL-6 ؉͞؉) littermates after the induction of AIA. Although all IL-6 ؉͞؉ mice developed severe arthritis, only mild arthritis was observed in IL-6 ؊͞؊ mice. Safranin O staining demonstrated that articular cartilage was well preserved in IL-6 ؊͞؊ mice, whereas it was destroyed completely in IL-6 ؉͞؉ mice. In addition, comparable mRNA expression for both IL-1␤ and tumor necrosis factor ␣, but not for IL-6, was detected in the inf lamed joints of IL-6 ؊͞؊ mice, suggesting that IL-6 may play a more crucial role in cartilage destruction than either IL-1␤ or tumor necrosis factor ␣. In immunological comparisons, both antigen-specific in vitro proliferative response in lymph node cells and in vivo antibody production were elicited in IL-6 ؊͞؊ mice, but they were reduced to less than half of that found in IL-6 ؉͞؉ mice. Lymph node cells of IL-6 ؊͞؊ mice produced many more Th2 cytokines than did IL-6 ؉͞؉ mice with either antigen-specific or nonspecific stimulation in in vitro culture. Taken together, these results indicate that IL-6 may play a key role in the development of AIA at the inductive as well as the effector phase, and the blockade of IL-6 is possibly beneficial in the treatment of rheumatoid arthritis.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Interleukin 6 plays a key role in the development of antigen-induced arthritis

Ohshima

Saeki²,

Mima³

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

364

240

View full text Add to dashboard Cite

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“…Intracellular PLA 2 s comprise the Ca 2ϩ -sensitive arachidonoyl-specific 85-kDa cytosolic PLA 2 and a number of Ca 2ϩ -independent PLA 2 s (5). In contrast, sPLA 2 s have several common characteristics including a relatively low molecular mass (13)(14)(15)(16)(17)(18), the presence of 6 -8 disulfide bridges, an absolute catalytic requirement for millimolar concentrations of Ca 2ϩ , and a broad specificity for phospholipids with different polar head groups and fatty acid chains (4,7). At present, five distinct sPLA 2 s have been identified in humans and classified into different groups (group IB, IIA, IID, V, and X) depending on the primary structure characterized by the number and positions of cysteine residues (7), while group IIC sPLA 2 found in rodents is a pseudogene in humans (8).…”

mentioning

confidence: 99%

Structures, Enzymatic Properties, and Expression of Novel Human and Mouse Secretory Phospholipase A2s

Suzuki

Ishizaki

Yokota

et al. 2000

Journal of Biological Chemistry

161

131

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Mammalian secretory phospholipase A 2 s (sPLA 2 s) form a family of structurally related enzymes that are involved in a variety of physiological and pathological processes via the release of arachidonic acid from membrane phospholipids or the binding to specific membrane receptors. Here, we report the cloning and characterization of a novel sPLA 2 that is the sixth isoform of the sPLA 2 family found in humans. The novel human mature sPLA 2 consists of 123 amino acids (M r ‫؍‬ 14,000) and is most similar to group IIA sPLA 2 (sPLA 2 -IIA) with respect to the number and positions of cysteine residues as well as overall identity (51%). Therefore, this novel sPLA 2 should be categorized into group II and called group IIE (sPLA 2 -IIE) following the recently identified group IID sPLA 2 (sPLA 2 -IID). The enzymatic properties of recombinant human sPLA 2 -IIE were almost identical to those of sPLA 2 -IIA and IID in terms of Ca 2؉ requirement, optimal pH, substrate specificity, as well as high susceptibility to the sPLA 2 inhibitor indoxam. Along with the biochemical properties of proteins, genetic and evolutional similarities were also observed among these three types of group II sPLA 2 s as to the chromosomal location of the human gene (1p36) and the exon/intron organization. The expression of sPLA 2 -IIE transcripts in humans was restricted to the brain, heart, lung, and placenta in contrast to broad expression profiles for sPLA 2 -IIA and -IID. In sPLA 2 -IIA-deficient mice, the expression of sPLA 2 -IIE was markedly enhanced in the lung and small intestine upon endotoxin challenge, which contrasted with the reduced expression of sPLA 2 -IID mRNA. In situ hybridization analysis revealed elevation of sPLA 2 -IIE mRNA at alveolar macrophage-like cells in the lung of endotoxin-treated mice. These findings suggest a distinct functional role of novel sPLA 2 -IIE in the progression of inflammatory processes.

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Kinetics of aggrecanase- and metalloproteinase-induced neoepitopes in various stages of cartilage destruction in murine arthritis

Meurs

Lent

Holthuysen

et al. 1999

Arthritis & Rheumatism

129

117

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Objective. Two major cleavage sites, one mediated by metalloproteinases (MMPs) and the other by an as-yet unidentified enzyme termed aggrecanase, have been observed in aggrecan. To learn more about the relative contribution of these enzymes during cartilage degradation, this study assessed the occurrence of both specific neoepitopes in cartilage during murine arthritis and examined the correlation between neoepitope formation and different aspects of cartilage damage.Methods. Reversible cartilage damage was induced in mice in the zymosan-induced arthritis (ZIA) model, partly irreversible cartilage damage in the antigen-induced arthritis (AIA) model, and irreversible, destructive cartilage damage in the collagen-induced arthritis (CIA) model. Immunolocalization techniques were used to detect the specific C-terminal neoepitopes VDIPEN (MMPs) and NITEGE (aggrecanase).Results. In normal cartilage from young adult mice, no VDIPEN epitopes were detected, but a limited amount of NITEGE epitopes were already present. During the early phase of proteoglycan (PG) depletion, NITEGE expression was raised substantially in all arthritis models. VDIPEN epitopes were not detected in this early phase of cartilage destruction. When PG depletion progressed toward advanced cartilage damage, VDIPEN epitopes were induced. During ZIA, minimal induction of VDIPEN was observed, whereas in AIA, strong, but partly reversible, VDIPEN staining was evident, and in CIA, an extensive presence and persistence of the MMP-induced neoepitope was seen. When VDIPEN epitopes were intensely present, NITEGE epitopes were greatly reduced at that site in the cartilage.Conclusion. Presence of VDIPEN epitopes in cartilage correlated with severe cartilage damage, but these epitopes were not detected during early PG degradation. This suggests a limited role for VDIPEN-inducing MMPs in early PG degradation during murine arthritis. In contrast, aggrecanase epitopes were induced before the appearance of VDIPEN epitopes, but they disappeared with progression of cartilage damage.

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Antigen‐induced arthritis in mice

Cited by 288 publications

References 25 publications

Interleukin 6 plays a key role in the development of antigen-induced arthritis

Interleukin 6 plays a key role in the development of antigen-induced arthritis

Structures, Enzymatic Properties, and Expression of Novel Human and Mouse Secretory Phospholipase A2s

Kinetics of aggrecanase- and metalloproteinase-induced neoepitopes in various stages of cartilage destruction in murine arthritis

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