Blockade of CCL24 with a monoclonal antibody ameliorates experimental dermal and pulmonary fibrosis (original) (raw)
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The Role of CCL24 in Systemic Sclerosis
Rambam Maimonides Medical Journal
Systemic sclerosis (SSc) is a chronic immune-mediated disease characterized by microangiopathy, immune dysregulation, and progressive fibrosis of the skin and internal organs. Though not fully understood, the pathogenesis of SSc is dominated by microvascular injury, endothelial dysregulation, and immune response that are thought to be associated with fibroblast activation and related fibrogenesis. Among the main clinical subsets, diffuse SSc (dSSc) is a progressive form with rapid and disseminated skin thickening accompanied by internal organ fibrosis and dysfunction. Despite recent advances and multiple randomized clinical trials in early dSSc patients, an effective disease-modifying treatment for progressive skin fibrosis is still missing, and there is a crucial need to identify new targets for therapeutic intervention. Eotaxin-2 (CCL24) is a chemokine secreted by immune cells and epithelial cells, which promotes trafficking of immune cells and activation of pro-fibrotic cells thr...
Clinical and experimental rheumatology
Chemokines favour leukocyte homing and participate actively in inflammation and accumulation of extracellular matrix. The aim of our work is to assess in patients with systemic sclerosis (SSc) the serum levels of CC chemokines: CCL2 monocyte chemotactic protein-1 (MCP-1/CCL2), CCL5 'regulated upon activation, normal T expressed and secreted' (RANTES/CCL5) and CCL3 'macrophage inflammatory protein 1 α' (MIP1α/CCL3), their associations with clinical characteristics and modulation by infusions of the prostaglandin E1 (PGE1) analogue, alprostadil alpha-cyclodextrin. Serum levels of MCP1/CCL2, RANTES/CCL5 and MIP1α/CCL3 were studied by ELISA in 40 patients with SSc (34 lSSc, 6 dSSc) before and after 3 consecutive daily PGE1 infusions (60 μg) and compared to 30 healthy controls. We recorded clinical (age, duration of disease, ulcers, teleangectasias, calcinosis, skin score [mRSS], capillaroscopy pattern, heart and lung involvement) and immunological characteristics (ANA/AC...
Arthritis research & therapy, 2018
Systemic sclerosis (SSc) is characterized by vasculopathy and progressive fibrosis. CTLA4-Ig (abatacept) is able to interact with the cell surface costimulatory molecule CD86 and downregulate the target cell. The aim of this study was to evaluate the in-vitro effects of CTLA4-Ig treatment on circulating fibrocytes and skin fibroblasts isolated from the same SSc patient. Circulating fibrocytes and skin fibroblasts were obtained from eight SSc patients with "limited" cutaneous involvement and from four healthy subjects (HSs). Samples were analyzed by fluorescence-activated cell sorter analysis (FACS) at baseline (T0) and after 8 days of culture (T8) for CD45, collagen type I (COL I), CXCR4, CD14, CD86, and HLA-DRII expression. Circulating fibrocytes were treated for 3 h and skin fibroblasts for 24/48 h with CTLA4-Ig (10, 50, 100, 500 μg/ml). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed for CD86, COL I, FN, TGFβ, αSMA, S100A4, CXCR2, CXCR4, CD11a, ...
The Journal of Rheumatology, 2012
Objective.We evaluated the effect of interferon-γ (IFN-γ) and/or tumor necrosis factor-α (TNF-α) on the secretion of prototype proinflammatory cytokine interleukin 6 (IL-6), compared to T-helper 1 [Th1; chemokine (C-X-C motif) ligand 10 (CXCL10)] or Th2 [chemokine (C-C motif) ligand 2 (CCL2)] chemokines, in primary cultured fibroblasts from patients with systemic sclerosis (SSc) at an early stage of the disease.Methods.Fibroblast cultures from 5 SSc patients (disease duration < 2 yrs) and 5 healthy controls were evaluated for the production of IL-6, CXCL10, and CCL2 at the basal level and after stimulation with IFN-γ and/or TNF-α.Results.SSc fibroblasts basally produced higher levels of IL-6 than controls, while no difference was observed about CCL2 and CXCL10. TNF-α was able to dose-dependently induce IL-6 and CCL2 secretion in SSc, but not in control fibroblasts. By stimulation with increasing doses of IFN-γ, SSc fibroblasts were induced to secrete CCL2 and CXCL10, while no eff...