Elevated substance p and accelerated cartilage degradation in rabbit knees injected with interleukin‐1 and tumor necrosis factor

O’Byrne, E. M.; Blancuzzi, V.; Wilson, Douglas E.; Wong, M.; Jeng, Arco Y.

doi:10.1002/art.1780330715

Cited by 87 publications

(39 citation statements)

References 25 publications

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“…Intra-articular injections of TNF and IL-1 cause an in¯ux of neutrophils into the joint and synovitis similar to that seen in experimental arthritis, but only IL-1 results in marked depletion of the cartilage matrix (Dingle et al, 1987b;Van De Loo & Van Den Berg, 1990;Henderson & Pettipher, 1989;O'byrne et al, 1990). In vitro, TNF is also less potent Berg et al, 1994;Williams et al, 1992;Piguet et al, 1992;Thorbecke et al, 1992).…”

Section: Introductionmentioning

confidence: 91%

Cloricromene, a coumarine derivative, protects against collagen‐induced arthritis in Lewis rats

Cuzzocrea

Mazzon

Bevilaqua

et al. 2000

British J Pharmacology

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1 The aim of the present study was to investigate the e ects of cloricromene, a coumarine derivative, in rats subjected to collagen-induced arthritis. 2 Collagen-induced arthritis (CIA) was induced in Lewis rats by an intradermal injection of 100 ml of the emulsion (containing 100 mg of bovine type II collagen) (CII) and complete Freund's adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. 3 Lewis rats developed an erosive hind paw arthritis when immunized with CII in CFA. Macroscopic clinical evidence of CIA ®rst appeared as peri-articular erythema and oedema in the hind paws. The incidence of CIA was 100% by day 27 in the CII challenged rats and the severity of CIA progressed over a 35-day period with radiographic evaluation revealing focal resorption of bone together with osteophyte formation in the tibiotarsal joint and soft tissue swelling. 4 The histopathology of CIA included erosion of the cartilage at the joint margins. Treatment of rats with cloricromene (10 mg kg 71 i.p. daily) starting at the onset of arthritis (day 23), delayed the development of the clinical signs at days 24 ± 35 and improved histological status in the knee and paw. 5 Immunohistochemical analysis for iNOS, COX-2, nitrotyrosine and for poly (ADP-ribose) synthetase (PARS) revealed a positive staining in in¯amed joints from collagen-treated rats. The degree of staining for iNOS, COX-2, nitrotyrosine and PARS were markedly reduced in tissue sections obtained from collagen-treated rats, which had received cloricromene. 6 Radiographic signs of protection against bone resorption and osteophyte formation were present in the joints of cloricromene-treated rat. 7 This study provides the ®rst evidence that cloricromene, a coumarine derivative, attenuates the degree of chronic in¯ammation and tissue damage associated with collagen-induced arthritis in the rat.

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Section: Introductionmentioning

confidence: 91%

Cloricromene, a coumarine derivative, protects against collagen‐induced arthritis in Lewis rats

Cuzzocrea

Mazzon

Bevilaqua

et al. 2000

British J Pharmacology

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“…In addition, recent findings indicate that LP, or at least its N-terminal domain, may function as a growth factor up-regulating the synthesis of aggrecan and type II collagen in cartilage (21)(22)(23)(24).…”

Section: In Brainmentioning

confidence: 99%

Genetic Rescue of Chondrodysplasia and the Perinatal Lethal Effect of Cartilage Link Protein Deficiency

Czipri

Otto

Cs‐Szabó

et al. 2003

Journal of Biological Chemistry

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The targeted disruption of cartilage link protein gene (Crtl1) in homozygous mice resulted in a severe chondrodysplasia and perinatal lethality. This raised the question of whether the abnormalities seen in Crtl1 null mice are all caused by the absence of link protein in cartilage or whether the deficiency of the protein in other tissues and organs contributed to the phenotype. To address this question we have generated transgenic mice overexpressing cartilage link protein under the control of a cartilage-specific promoter, and then these transgenic mice were used for a genetic rescue of abnormalities in Crtl1 null mice. While the overexpression of cartilage link protein resulted in no abnormal phenotype, the cartilage-specific transgene expression of link protein could completely prevent the perinatal mortality of link protein-deficient mice and, depending on the level of the link protein expression, rescue skeletal abnormalities. Although link protein was originally isolated from cartilage, we found and determined Crtl1 transcripts and corresponding proteins in every organ tested from mouse embryos to aging animals. We also identified three additional members of the link protein family, all co-localized with hyaluronic acid-binding proteoglycans in the mouse genome. The ubiquitous presence of link protein suggests a general and systemic function of link protein in the organization of extracellular matrix in a number of tissues, possibly interacting with other proteoglycans, such as versican, brevican, and neurocan.A highly specific macromolecular organization of cartilage extracellular matrix (ECM) 1 is required for chondrogenesis, chondrocyte differentiation, endochondral ossification, and for the maintenance of the weight-bearing function of articular cartilage. The major macromolecular components of this ECM are the proteoglycan aggrecan, hyaluronic acid (hyaluronan, HA), link protein (LP) and type II collagen. Hundreds of aggrecan molecules associate with a single HA filament to form large proteoglycan aggregates. The link protein, a glycoprotein, binding simultaneously to both HA and aggrecan, stabilizes the aggregate structure (1), and the aggregates are entrapped within the mesh-like network of type II collagen fibrils (2-4). The negatively charged glycosaminoglycan chains of aggrecan bind large amounts of water and are responsible for the resiliency of cartilage (5). Mutation in a gene encoding components of cartilage ECM may result in skeletal disorders, chondrodysplasias, in mice (6, 7) and humans (8).Cartilage LP is a member of the hyaluronectin superfamily, and shares a high degree of sequence homology in different species, particularly in the HA binding domain (2), also known as "link module" (4, 9). Although LP was originally isolated from cartilage, its presence has been reported in numerous non-cartilaginous tissues, such as aorta (10), mesonephros, and other embryonic tissues (11, 12), brain (13) and sclera (14) in chicken, and the mouse cumulus-oocyte complex, without concomitant expression...

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“…In addition, our laboratory has recently demonstrated a novel mechanism by which substance P may augment inflammatory responses by dramatically diminishing the production of the immunosuppressive cytokine, TGF-␤1, from macrophages stimulated with LPS or IFN-␥ (22). Furthermore, compelling evidence for the importance of substance P and its receptor in inflammatory events in vivo comes from studies that have identified increased substance P levels (23)(24)(25)(26)(27)(28) or substance P receptor expression (29 -31) at sites of inflammation. More recently, studies have demonstrated greatly reduced inflammatory responses in genetically manipulated mice devoid of substance P/substance P receptor interactions (32,33), providing further evidence for this neuropeptide as a proinflammatory mediator in vivo.…”

Section: Il-4 and Ifn-␥ Up-regulatementioning

confidence: 99%

IL-4 and IFN-γ Up-Regulate Substance P Receptor Expression in Murine Peritoneal Macrophages

Marriott

Bost

2000

The Journal of Immunology

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While the ability of macrophages to express authentic substance P receptors (i.e., NK-1 receptors) has been inferred from radioreceptor binding assays and functional assays and, most recently, by identification of NK-1 receptor mRNA expression, we know little about NK-1 expression at the protein level or what host factors might up-regulate expression of this receptor. In the present study we demonstrate that the cytokines IL-4 and IFN-γ can increase the expression of NK-1 receptors on murine peritoneal macrophages. Specifically, we show that IL-4 and IFN-γ can elicit increases in the level of mRNA encoding the NK-1 receptor by up to 12- and 13-fold, respectively. Furthermore, these cytokines can significantly increase the expression of the NK-1 receptor protein as measured by Western blot and FACS analysis using specific Abs developed in our laboratory. In addition, we have demonstrated the ability of both IL-4 and IFN-γ to enhance the ability of macrophages to bind substance P as measured by radiolabeled binding assay. The observation that the level of expression of this receptor protein can be enhanced by cytokines that promote either cell-mediated (Th1) or humoral (Th2) immune responses supports the idea that this receptor can be induced during either type of immune response. As such, these results may point to a more ubiquitous role for substance P in the generation of optimal immune responses than previously appreciated.

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Elevated substance p and accelerated cartilage degradation in rabbit knees injected with interleukin‐1 and tumor necrosis factor

Cited by 87 publications

References 25 publications

Cloricromene, a coumarine derivative, protects against collagen‐induced arthritis in Lewis rats

Cloricromene, a coumarine derivative, protects against collagen‐induced arthritis in Lewis rats

Genetic Rescue of Chondrodysplasia and the Perinatal Lethal Effect of Cartilage Link Protein Deficiency

IL-4 and IFN-γ Up-Regulate Substance P Receptor Expression in Murine Peritoneal Macrophages

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