Interleukin-4 suppression of interleukin-1-induced transcription of collagenase (MMP-1) and stromelysin 1 (MMP-3) in human synovial fibroblasts

Borghaei, Ruth C.; Rawlings, P.Lyle; Mochan, Eugene

doi:10.1002/1529-0131(199808)41:8<1398::aid-art8>3.0.co;2-b

Cited by 50 publications

(36 citation statements)

References 41 publications

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“…First, ex vivo studies of synovial cell cultures or synovial tissue explants from RA patients have established that IL-4 and IL-13 exert antiinflammatory effects related to direct inhibition of proinflammatory mediators such as IL-1, TNF, IL-6, and GM-CSF, 35,36 MMP-1 and MMP-3. 37 These anti-inflammatory properties have also been demonstrated in vivo in CIA 16,30 and in the TNF-transgenic mouse model. 17 Second, IL-4 can increase the production of IL-1ra, 35 IL-1RII 38 and TNF receptor, 39 thus directly blocking the proinflammatory effects of IL-1 or TNF.…”

Section: Discussionmentioning

confidence: 88%

Adeno-associated virus-mediated delivery of IL-4 prevents collagen-induced arthritis

et al. 2000

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Immunomodulation of autoimmune inflammatory diseases like rheumatoid arthritis can be achieved by anti-inflammatory T2 cytokines such as interleukin (IL)-4 administered by gene therapy. In this study we investigated the efficiency of adeno-associated viruses (AAV) vectors in collagen-induced arthritis (CIA). After injection of AAV-LacZ in the tarsus area of mice, the expression of the transgene was localized in the deep muscles cells near the bone. LacZ expression was found in liver, heart and lung after i.m. injection of AAV-LacZ, showing a spread of the vector over the body. Anti-AAV neutralizing antibodies were detected in the serum after i.m. injection of AAV-LacZ, but they did not alter the transgene

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Section: Discussionmentioning

confidence: 88%

Adeno-associated virus-mediated delivery of IL-4 prevents collagen-induced arthritis

et al. 2000

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“…In agreement with these data, we observed an accumulation of MMP-2 and -9 in fetal hepatocytes treated with LPS and HGF. In addition to fetal hepatocytes, the regulation of the expression of MMPs has been described through a PGE 2 -cAMP-dependent pathway in monocytes, 21 sinovial fibroblasts 33 and vascular endothelial cells. 34 Taken together, these results suggest that COX-2 expression and PG synthesis are key components in the secretion of MMPs, and therefore in the remodeling of ECM.…”

Section: Discussionmentioning

confidence: 99%

Expression of Cyclooxygenase–2 Promotes the Release of Matrix Metalloproteinase–2 and –9 in Fetal Rat Hepatocytes

Callejas

2001

Hepatology

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Treatment of primary cultures of fetal hepatocytes with proinflammatory cytokines, lipopolysaccharide (LPS), and hepatocyte growth factor promoted the expression of cyclooxygenase-2 (COX-2) and the synthesis of high amounts of prostaglandins (PGs). Under these conditions, the active forms of the matrix metalloproteinases-2 and -9 (MMPs) were released to the extracellular medium. This process was inhibited when the synthesis of PGs was suppressed pharmacologically with COX-2 inhibitors. Addition to the cell cultures of PGE 2 promoted the release of MMPs through a mechanism that involved the expression of COX-2 and the synthesis of additional PGs. Kinetic analysis of the secretion of MMPs in response to LPS and PGE 2 showed a similar time course, with a lag period of 6 hours, which suggests that PGE 2 does not act directly on the mechanism of MMP processing and release. Inhibitors of protein kinase A, p38 MAP kinase, phosphatidylinositol-3-kinase, and nuclear factor B Prostaglandin H synthase, also known as cyclooxygenase (COX), catalyzes the synthesis of prostaglandin H 2 from arachidonate and constitutes a key regulatory step in the biosynthesis of prostanoids. 1-3 Two distinct isoforms of COX are known: COX-1 and COX-2. The two isoenzymes are encoded by different genes, and the control of their expression, regulation of enzyme activity, and physiologic functions are very different. 1,4 COX-1 seems to be involved in the house keeping function of prostaglandins (PGs) 4 and is expressed constitutively. In contrast, COX-2 is inducible, is expressed as an immediate early gene, and is involved in the onset of inflammation and mitogenic responses. 1,3,5,6 COX-2 expression is positively regulated by lipopolysaccharide (LPS), interleukin 1␤, tumor necrosis factor ␣, and reactive oxygen intermediates in different cells. 7,8 In addition to these stimuli, it has been described that hepatocyte growth factor (HGF) and epidermal growth factor (EGF) triggered the expression of COX-2 in rat gastric epithelial cells, in human amnion-derived WISH cells, and in human gingival fibroblasts, and this effect was mediated through the activation of the ERK2 signaling pathway. [9][10][11] Our previous results showed that adult hepatocytes failed to express COX-2 regardless of the proinflammatory factors used. However, fetal hepatocytes, which exhibit a liver phenotype distinct from the adult counterpart, were able to express COX-2 upon challenge with LPS and proinflammatory cytokines. 8 Regarding the mechanism responsible for the suppression of COX-2 inducibility in adult hepatocytes, our data suggest the existence of a close relationship between COX-2 induction and the decrease of C/EBP␣ levels that bind to the nuclear factor-interleukin 6 site of the COX-2 promoter. 12 In addition to inflammation and cell growth regulation, COX-2 expression has been associated with carcinogenesis and tumor development. 3,6 Several population-based studies have detected a 40% to 50% decrease in relative risk for colorectal cancer in persons who regularl...

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“…Proliferation of the synovium is associated with increased production of proinflammatory cytokines, including IL-1 and TNF-␣, which play a crucial role in cartilage degradation through their inducing effects on matrix metalloproteinases. IL-4 is able to suppress detrimental effects of IL-1 and TNF-␣ by stimulating IL-1Ra production (1), and down-regulating TNF receptor (2), transcription of metalloproteinases (3), and synoviocyte proliferation (4). These effects could be exploited in the treatment of RA and/or osteoarthritis (OA).…”

Section: R Heumatoid Arthritis (Ra)mentioning

confidence: 99%

IL-4 and IL-13, But Not IL-10, Protect Human Synoviocytes from Apoptosis

Relić

Guicheux

Mézin

et al. 2001

The Journal of Immunology

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Interleukin-4, which has been contemplated for the treatment of rheumatoid arthritis and/or osteoarthritis because of its anticatabolic properties, has also been shown to modulate apoptosis. Because inadequate apoptosis is thought to contribute to synovial hyperplasia, we have investigated the ability of IL-4 and other Th2 cytokines to protect human synovial cells from apoptosis. Human synoviocytes or synovial explants were pretreated with IL-4, IL-10, and IL-13 before exposure to NO donor sodium-nitro-prusside (SNP). Apoptosis was evaluated by microscopy, annexin V-FITC, 3-(4,5-dimethylthiazol-2-gl)-5-(3-carboxymethoxylphenyl)-2-(4-sulphophenyl-2H tetrazolium inner salt (MTS) test, pulse field gel electrophoresis, and a method proposed in this study based on 32P Klenow end labeling of high m.w. DNA. Pretreatment by IL-4 or IL-13, but not IL-10, protected human synoviocytes from apoptosis induced by SNP. Even at doses as high as 2 mM SNP, up to 86% and 56% protection was achieved, after IL-4 and IL-13 treatment, respectively. Cell survival was dependent on IL concentration. IL-4 and IL-13 also had antiapoptotic effects on SNP-treated human synovial explants. Effects of IL-4 and IL-13 varied in the presence of phosphatidylinositol-3 kinase and protein kinase C inhibitors, implying the involvement of these pathways in antiapoptotic signaling. Antiapoptotic effects were dramatically inhibited by LY294002, and partially by the protein kinase C inhibitor Gö 6976, while insulin-like growth factor increased synoviocyte survival. The possibility that IL-4 and IL-13 may enhance synovial expansion in vivo by their antiapoptotic effects is discussed.

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Interleukin-4 suppression of interleukin-1-induced transcription of collagenase (MMP-1) and stromelysin 1 (MMP-3) in human synovial fibroblasts

Cited by 50 publications

References 41 publications

Adeno-associated virus-mediated delivery of IL-4 prevents collagen-induced arthritis

Adeno-associated virus-mediated delivery of IL-4 prevents collagen-induced arthritis

Expression of Cyclooxygenase–2 Promotes the Release of Matrix Metalloproteinase–2 and –9 in Fetal Rat Hepatocytes

IL-4 and IL-13, But Not IL-10, Protect Human Synoviocytes from Apoptosis

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