TIMPs and MMPs expression in CSF from patients with TSP/HAM

Kettlun, Ana M.; Cartier, Luis; Garcı́a, Lorena; Collados, L.; Vásquez, F; Ramı́rez, Eugenio; Valenzuela, Manuel

doi:10.1016/s0024-3205(03)00146-2

Cited by 18 publications

(14 citation statements)

References 36 publications

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“…Interestingly, upregulation of TIMP4 in response to inflammation is not restricted to vascular tissue. In fact, similar findings have been described in inflamed joints (Celiker et al 2002) and in cerebrospinal fluid from patients with tropical spastic paraparesis or myelopathy associated with human T cell lymphotrophic virus (Kettlun et al 2003). Furthermore, Fig.…”

Section: Discussionsupporting

confidence: 85%

Tissue inhibitor of metalloproteinases 4 (TIMP4) is involved in inflammatory processes of human cardiovascular pathology

Koskivirta

Rahkonen

Mäyränpää

et al. 2006

Histochem Cell Biol

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Tissue inhibitors of matrix metalloproteinases (TIMPs) comprise a family of four members, of which TIMP4 is characterized by being primarily restricted to cardiovascular structures. We demonstrate with immunohistochemical analysis of healthy human tissue that TIMP4 is present in medial smooth muscle cells and adventitial capillaries of arteries as well as in cardiomyocytes. Animal studies have suggested a role for TIMP4 in several inflammatory diseases and cardiovascular pathologies. We therefore examined whether TIMP4 is involved in human inflammatory cardiovascular disorders, specifically atherosclerosis, giant cell arteritis and chronic rejection of heart allografts. TIMP4 was most clearly visible in cardiovascular tissue areas populated by abundant inflammatory cells, mainly macrophages and CD3+ T cells. Using western blotting and immunocytochemistry, human blood derived lymphocytes, monocytes/macrophages and mast cells were shown to produce TIMP4. In advanced atherosclerotic lesions, TIMP4 was detected around necrotic lipid cores, whereas TIMP3 and caspase 3 resided within and around the core regions, indicating different roles for TIMP3 and TIMP4 in inflammation-induced apoptosis and in matrix turnover. In conclusion, the data demonstrate upregulation of TIMP4 in human cardiovascular disorders exhibiting inflammation, suggesting its future use as a novel systemic marker for vascular inflammation.

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Section: Discussionsupporting

confidence: 85%

Tissue inhibitor of metalloproteinases 4 (TIMP4) is involved in inflammatory processes of human cardiovascular pathology

Koskivirta

Rahkonen

Mäyränpää

et al. 2006

Histochem Cell Biol

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“…Previous studies have shown that changes in MMP9 and/or TIMP1, IL-1β and IL-10 levels are associated with neuroinflammation and possibly with AD pathogenesis (Asahina et al, 2001; Benzing et al, 1999; Dzwonek et al, 2004; Frank-Cannon et al, 2009; Gardner and Ghorpade, 2003; Kettlun et al, 2003; Koronyo-Hamaoui et al, 2009; Remarque et al, 2001; Shaftel et al, 2008; Strle et al, 2001). Thus, the apoE4-185 induced MMP9/TIMP1 imbalance in both SK-N-SH and SW-1783 cells and IL-1β increase and IL-10 decrease in SK-N-SH cells suggest that specific apoE4 proteolytic fragments may affect inflammatory processes in brain cells and may participate in neuroinflammation and AD.…”

Section: Discussionmentioning

confidence: 99%

An apolipoprotein E4 fragment affects matrix metalloproteinase 9, tissue inhibitor of metalloproteinase 1 and cytokine levels in brain cell lines

et al. 2012

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Apolipoprotein (apo) E4 isoform, a major risk factor for Alzheimer’s disease (AD), is more susceptible to proteolysis than apoE2 and apoE3 isoforms. ApoE4 fragments have been found in AD patients’ brain. In the present study, we examined the effect of full-length apoE4 and apoE4 fragments apoE4[Δ(186-299)] and apoE4[Δ(166-299)] on inflammation in human neuroblastoma SK-N-SH and human astrocytoma SW-1783 cells. Western blot and zymography analysis showed that treatment of SK-N-SH cells with apoE4[Δ(186-299)], but not full-length apoE4 or the shorter apoE4[Δ(166-299)] fragment, leads to increased extracellular levels of matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 1 (TIMP1). Real-time PCR showed that interleukin (IL)-1β gene expression is also increased in SK-N-SH cells treated with apoE4[Δ(186-299)]. Treatment of SK-N-SH cells with IL-1β leads to increased MMP9 and TIMP1 extracellular levels, suggesting that the induction of IL-1β may be the mechanism by which apoE4[Δ(186-299)] regulates MMP9 and TIMP1 levels in these cells. In contrast to SK-N-SH cells, treatment of SW-1783 cells with apoE4[Δ(186-299)] and to a lesser extent with apoE4, leads to increased TIMP1 extracellular levels without affecting MMP9 levels, Additionally, apoE4[Δ(186-299)] leads to decreased IL-10 gene expression in SK-N-SH cells, while both apoE4 and apoE4[Δ(186-299)] lead to decreased TNFα gene expression without affecting IL-1β and IL-10 gene expression in SW-1783 cells. Overall, our findings indicate that a specific apoE4 fragment (apoE4[Δ(186-299)]), with molecular mass similar that of apoE4 fragments detected in AD patients’ brain, can influence the level of inflammatory molecules in brain cell lines. It is possible that these phenomena contribute to AD pathogenesis.

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“…They have also been observed in inflammatory pathologies of the child, as in chronic suppurative otitis media and in chronic lung diseases (Ekekezie et al, 2004;Jang et al, 2006). Both gelatinases have ben found in a variety of body fluids, namely, caphaloraquid fluid, tracheal secretion, middle ear secretion, gingival fluid, blood plasma and saliva (Ekekezie et al, 2004;Jang et al, 2006;Kettlun et al, 2003;Schulz et al, 2004;Valenzuela, 2000;Wu et al, 1997). Patients subjected to therapeutical irradiation of the maxillofacial territory have active and inactive forms of MMP-2 and MMP-9 in saliva and irradiation would increase the MMP-9 activity (Vuotila et al, 2002).…”

Section: Occurrence Of Molecules Associated With Extracellular Matrixmentioning

confidence: 99%

Infantile Chronic Recurrent Parotitis (ICRP): Analysis of Changes in the Expression of Parotid Salivary Proteins Associated with the Disease

Morales-Bozo¹,

Orellana²,

Mendoza³

2012

Contemporary Pediatrics

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TIMPs and MMPs expression in CSF from patients with TSP/HAM

Cited by 18 publications

References 36 publications

Tissue inhibitor of metalloproteinases 4 (TIMP4) is involved in inflammatory processes of human cardiovascular pathology

Tissue inhibitor of metalloproteinases 4 (TIMP4) is involved in inflammatory processes of human cardiovascular pathology

An apolipoprotein E4 fragment affects matrix metalloproteinase 9, tissue inhibitor of metalloproteinase 1 and cytokine levels in brain cell lines

Infantile Chronic Recurrent Parotitis (ICRP): Analysis of Changes in the Expression of Parotid Salivary Proteins Associated with the Disease

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