Interactions entre la Fibrilline-1 et le TGF-β

Wipff, Julien; Allanore, Yannick; Boileau, Cathérine

doi:10.1051/medsci/2009252161

Cited by 13 publications

(4 citation statements)

References 29 publications

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“…The median age of controls (four females and one male) was 57 years (range 31 to 62 years). All of the study aspects were approved by the local ethics review committee (Comité Consultatif de Protection des Personnes dans la Recherche Biomédicale Paris Ile de France III), and written informed consent was obtained from all patients and controls [9, 19, 20]. …”

Section: Methodsmentioning

confidence: 99%

Targeting IL-6 by both passive or active immunization strategies prevents bleomycin-induced skin fibrosis

et al. 2014

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IntroductionInterleukin-6 (IL-6) is a pleiotropic cytokine for which preliminary data have suggested that it might contribute to systemic sclerosis (SSc). Our aims were to investigate, firstly, IL-6 expression in patients with SSc and, secondly, the efficacy of both passive and active immunization against IL-6 to reduce skin fibrosis in complementary mouse models of SSc.MethodsHuman serum levels and skin expression of IL-6 were determined by enzyme-linked immunosorbent assay and immunohistochemistry, respectively. We first evaluated the antifibrotic properties of the monoclonal anti-IL-6R antibody, MR16-1, in the bleomycin-induced dermal fibrosis mouse model, reflecting early and inflammatory stages of SSc. Then, we assessed the efficacy of MR16-1 in tight skin-1 (Tsk-1) mice, an inflammation-independent model of skin fibrosis. Additionally, we have developed an innovative strategy using an anti-IL-6 peptide-based active immunization. Infiltrating leukocytes, T cells, and B cells were quantified, and IL-6 levels were measured in the serum and lesional skin of mice after passive or active immunization.ResultsSerum and skin levels of IL-6 were significantly increased in patients with early SSc. Treatment with MR16-1 led in the bleomycin mouse model to a 25% (P = 0.02) and 30% (P = 0.007) reduction of dermal thickness and hydroxyproline content, respectively. MR16-1 demonstrated no efficacy in Tsk-1 mice. Thereafter, mice were immunized against a small peptide derived from murine IL-6 and this strategy led in the bleomycin model to a 20% (P = 0.02) and 25% (P = 0.005) decrease of dermal thickness and hydroxyproline content, respectively. Passive and active immunization led to decreased T-cell infiltration in the lesional skin of mice challenged with bleomycin. Upon bleomycin injections, serum and skin IL-6 levels were increased after treatment with MR16-1 and were significantly reduced after anti-IL-6 active immunization.ConclusionsOur results support the relevance of targeting IL-6 in patients with early SSc since IL-6 is overexpressed in early stages of the disease. Targeting IL-6 by both passive and active immunization strategies prevented the development of bleomycin-induced dermal fibrosis in mice. Our results highlight the therapeutic potential of active immunization against IL-6, which is a seductive alternative to passive immunization.

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Section: Methodsmentioning

confidence: 99%

Targeting IL-6 by both passive or active immunization strategies prevents bleomycin-induced skin fibrosis

et al. 2014

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“…In SSc, abnormal remodeling of ECM results in fibrosis characterized by excessive production and deposit of ECM substances: these disturbances are, at least in part, related to activation of TGF-ß. A growing body of evidence supports a close relationship between fibrillin-1 and TGF-ß and several studies suggest that SSc may belong among the fibrillinopathies 3 . In this context, remodeling of the microfibrillar network in SSc could contribute to TGF-ß overactivation.…”

Section: Discussionmentioning

confidence: 99%

Association of Metalloproteinase Gene Polymorphisms with Systemic Sclerosis in the European Caucasian Population

Wipff

Dieudé²,

Avouac³

et al. 2010

J Rheumatol

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“…Additional IP assays with an anti-FBN1 antibody are needed to further test the interaction of p42 with endogenous FBN1. FBN1 is an extracellular matrix glycoprotein that can downregulate the transforming growth factor beta (TGF-β) signaling pathway [34][35][36]. Previous publications have reported OAS activity in the serum, and showed that extracellular OAS1 could enter cells and exert an antiviral activity independent of RNase L [37][38][39].…”

Section: Discussionmentioning

confidence: 99%

Characteristics of Human OAS1 Isoform Proteins

Han

Elbahesh

Brinton

2020

Viruses

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The human OAS1 (hOAS1) gene produces multiple possible isoforms due to alternative splicing events and sequence variation among individuals, some of which affect splicing. The unique C-terminal sequences of the hOAS1 isoforms could differentially affect synthetase activity, protein stability, protein partner interactions and/or cellular localization. Recombinant p41, p42, p44, p46, p48, p49 and p52 hOAS1 isoform proteins expressed in bacteria were each able to synthesize trimer and higher order 2′-5′ linked oligoadenylates in vitro in response to poly(I:C). The p42, p44, p46, p48 and p52 isoform proteins were each able to induce RNase-mediated rRNA cleavage in response to poly(I:C) when overexpressed in HEK293 cells. The expressed levels of the p42 and p46 isoform proteins were higher than those of the other isoforms, suggesting increased stability in mammalian cells. In a yeast two-hybrid screen, Fibrillin1 (FBN1) was identified as a binding partner for hOAS1 p42 isoform, and Supervillin (SVIL) as a binding partner for the p44 isoform. The p44-SVIL interaction was supported by co-immunoprecipitation data from mammalian cells. The data suggest that the unique C-terminal regions of hOAS1 isoforms may mediate the recruitment of different partners, alternative functional capacities and/or different cellular localization.

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Interactions entre la Fibrilline-1 et le TGF-β

Cited by 13 publications

References 29 publications

Targeting IL-6 by both passive or active immunization strategies prevents bleomycin-induced skin fibrosis

Targeting IL-6 by both passive or active immunization strategies prevents bleomycin-induced skin fibrosis

Association of Metalloproteinase Gene Polymorphisms with Systemic Sclerosis in the European Caucasian Population

Characteristics of Human OAS1 Isoform Proteins

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