Molecular and cellular mediators of interleukin-1-dependent acute inflammatory arthritis

Lawlor, Kate E.; Campbell, Ian K.; O’Donnell, Kristy; Wu, Li; Wicks, Ian P.

doi:10.1002/1529-0131(200102)44:2<442::aid-anr63>3.0.co;2-m

Cited by 51 publications

(19 citation statements)

References 36 publications

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“…It is noteworthy that the pain arising from exogenous TNF administration to the paw and to the mBSA-injected joint is dependent on the same pathway as well as on a contribution from a COX-2-dependent product(s). We have previously found that the mBSA/IL-1 arthritis model, which is driven by s.c. IL-1, is also GM-CSF dependent (25,43) but, unlike the mBSA/TNF model, is T cell dependent (44), indicating that there are alternative pathways leading to a GM-CSF requirement. Interestingly, in the mBSA/TNF arthritis model, pain development, as measured by the incapacitance meter, was detected at 6 hours after s.c. TNF administration, which is faster than that developed in the mBSA arthritis models driven by s.c. IL-1, GM-CSF, and CCL17, in which it takes 2 to 5 days before pain can be detected using the same method (23,25).…”

Section: Discussionmentioning

confidence: 91%

TNF and granulocyte macrophage-colony stimulating factor interdependence mediates inflammation via CCL17

et al. 2018

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TNF and granulocyte macrophage-colony stimulating factor (GM-CSF) have proinflammatory activity and both contribute, for example, to rheumatoid arthritis pathogenesis. We previously identified a new GM-CSF→JMJD3 demethylase→interferon regulatory factor 4 (IRF4)→CCL17 pathway that is active in monocytes/macrophages in vitro and important for inflammatory pain, as well as for arthritic pain and disease. Here we provide evidence for a nexus between TNF and this pathway, and for TNF and GM-CSF interdependency. We report that the initiation of zymosan-induced inflammatory pain and zymosan-induced arthritic pain and disease are TNF dependent. Once arthritic pain and disease are established, blockade of GM-CSF or CCL17, but not of TNF, is still able to ameliorate them. TNF is required for GM-CSF-driven inflammatory pain and for initiation of GM-CSF-driven arthritic pain and disease, but not once they are established. TNF-driven inflammatory pain and TNF-driven arthritic pain and disease are dependent on GM-CSF and mechanistically require the same downstream pathway involving GM-CSF→CCL17 formation via JMJD3-regulated IRF4 production, indicating that GM-CSF and CCL17 can mediate some of the proinflammatory and algesic actions of TNF. Given we found that TNF appears important only early in arthritic pain and disease progression, targeting a downstream mediator, such as CCL17, which appears to act throughout the course of disease, could be effective at ameliorating chronic inflammatory conditions where TNF is implicated.

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Section: Discussionmentioning

confidence: 91%

TNF and granulocyte macrophage-colony stimulating factor interdependence mediates inflammation via CCL17

et al. 2018

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“…Clinical symptoms include pain, swelling, joint enlargement and decreased range of joint motion. Substantial evidence confirms the role of proinflammatory cytokines, including IL-1β, as mediators in disease development [20-22]. To explore whether osteoarthritis contributes to the development of neuroinflammation and possibly AD pathology, we employed somatic mosaic expression of IL-1β in the knees and temporomandibular joints of the Col-IL1β XAT transgenic mouse model of osteoarthritis [23-25].…”

Section: Introductionmentioning

confidence: 99%

Osteoarthritis accelerates and exacerbates Alzheimer's disease pathology in mice

Kyrkanides

Tallents

Miller

et al. 2011

J Neuroinflammation

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BackgroundThe purpose of this study was to investigate whether localized peripheral inflammation, such as osteoarthritis, contributes to neuroinflammation and neurodegenerative disease in vivo.MethodsWe employed the inducible Col1-IL1βXAT mouse model of osteoarthritis, in which induction of osteoarthritis in the knees and temporomandibular joints resulted in astrocyte and microglial activation in the brain, accompanied by upregulation of inflammation-related gene expression. The biological significance of the link between peripheral and brain inflammation was explored in the APP/PS1 mouse model of Alzheimer's disease (AD) whereby osteoarthritis resulted in neuroinflammation as well as exacerbation and acceleration of AD pathology.ResultsInduction of osteoarthritis exacerbated and accelerated the development of neuroinflammation, as assessed by glial cell activation and quantification of inflammation-related mRNAs, as well as Aβ pathology, assessed by the number and size of amyloid plaques, in the APP/PS1; Col1-IL1βXAT compound transgenic mouse.ConclusionThis work supports a model by which peripheral inflammation triggers the development of neuroinflammation and subsequently the induction of AD pathology. Better understanding of the link between peripheral localized inflammation, whether in the form of osteoarthritis, atherosclerosis or other conditions, and brain inflammation, may prove critical to our understanding of the pathophysiology of disorders such as Alzheimer's, Parkinson's and other neurodegenerative diseases.

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“…injection of saline only, then 7 days after i.a. injection, the joints appear normal, even when IL-1β is given subcutaneously [25]. To determine how the different elicitation protocols may explain these opposite results in u-PA -/- mice, we used an approach similar to that of Li and colleagues [21] but combined the systemic K/BxN arthritis model with an i.a.…”

Section: Resultsmentioning

confidence: 99%

“…This arthritis development following i.a. injection of only saline, which by itself does not lead to arthritis [25], could be due to the prior presence of the GPI (glucose-6-phosphate isomerase) antibodies and their immune complexes in the injected joint (from the K/BxN serum transfer [32]), contributing to the prolongation of the normally acute inflammatory response associated with the trauma of the injection and leading subsequently to arthritis development in that joint. Since cartilage proteoglycan loss and bone erosions were now observed in the joint receiving the i.a.…”

Section: Discussionmentioning

confidence: 99%

Urokinase-type plasminogen activator and arthritis progression: contrasting roles in systemic and monoarticular arthritis models

et al. 2010

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IntroductionUrokinase-type plasminogen activator (u-PA) has been implicated in tissue destruction/remodeling. The absence of u-PA results in resistance of mice to systemic immune complex-driven arthritis models; monoarticular arthritis models involving an intra-articular (i.a.) antigen injection, on the other hand, develop more severe arthritis in its absence. The aims of the current study are to investigate further these contrasting roles that u-PA can play in the pathogenesis of inflammatory arthritis and to determine whether u-PA is required for the cartilage and bone destruction associated with disease progression.MethodsTo determine how the different pathogenic mechanisms leading to arthritis development in the different models may explain the contrasting requirement for u-PA, the systemic, polyarticular, immune complex-driven K/BxN arthritis model was modified to include an i.a. injection of saline as a local trauma in u-PA-/- mice. This modified model and the antigen-induced arthritis (AIA) model were also used in u-PA-/- mice to determine the requirement for u-PA in joint destruction. Disease severity was determined by clinical and histologic scoring. Fibrin(ogen) staining and the matrix metalloproteinase (MMP)-generated neoepitope DIPEN staining were performed by immunohistochemistry. Gene expression of inflammatory and destructive mediators was measured in joint tissue by quantitative PCR.ResultsIn our modified arthritis model, u-PA-/- mice went from being resistant to arthritis development following K/BxN serum transfer to being susceptible following the addition of an i.a. injection of saline. u-PA-/- mice also developed more sustained AIA compared with C57BL/6 mice, including reduced proteoglycan levels and increased bone erosions, fibrin(ogen) deposition and DIPEN expression. Synovial gene expression of the proinflammatory mediators (TNF and IL-1β), aggrecanases (ADAMTS-4 and -5) and MMPs (MMP3 and MMP13) were all sustained over time following AIA induction in u-PA-/- mice compared with C57BL/6 mice.ConclusionsWe propose that u-PA has a protective role in arthritis models with 'wound healing-like' processes following local trauma, possibly through u-PA/plasmin-mediated fibrinolysis, but a deleterious role in systemic models that are critically dependent on immune complex formation and complement activation. Given that cartilage proteoglycan loss and bone erosions were present and sustained in u-PA-/- mice with monoarticular arthritis, it is unlikely that u-PA/plasmin-mediated proteolysis is contributing directly to this tissue destruction/remodeling.

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Molecular and cellular mediators of interleukin-1-dependent acute inflammatory arthritis

Cited by 51 publications

References 36 publications

TNF and granulocyte macrophage-colony stimulating factor interdependence mediates inflammation via CCL17

TNF and granulocyte macrophage-colony stimulating factor interdependence mediates inflammation via CCL17

Osteoarthritis accelerates and exacerbates Alzheimer's disease pathology in mice

Urokinase-type plasminogen activator and arthritis progression: contrasting roles in systemic and monoarticular arthritis models

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