Blockade of CCL24 with a monoclonal antibody ameliorates experimental dermal and pulmonary fibrosis.
Animals
Antibodies, Monoclonal
/ pharmacology
Cell Differentiation
Cells, Cultured
Chemokine CCL24
/ antagonists & inhibitors
Disease Models, Animal
Female
Fibroblasts
/ metabolism
Fibrosis
/ drug therapy
Humans
Male
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Knockout
Polysaccharides, Bacterial
/ immunology
Pulmonary Fibrosis
/ drug therapy
Scleroderma, Systemic
/ drug therapy
Skin
/ drug effects
chemokines
inflammation
pulmonary fibrosis
systemic sclerosis
Journal
Annals of the rheumatic diseases
ISSN: 1468-2060
Titre abrégé: Ann Rheum Dis
Pays: England
ID NLM: 0372355
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
27
01
2019
revised:
11
05
2019
accepted:
14
05
2019
pubmed:
28
5
2019
medline:
1
4
2020
entrez:
27
5
2019
Statut:
ppublish
Résumé
We aimed to assess the expression of the CCL24 chemokine in systemic sclerosis (SSc) and to evaluate the possible pathogenic implications of the CCL24/CCR3 axis using both in vitro and in vivo models. We further investigated the efficacy of an anti-CCL24 monoclonal antibody (mAb), CM-101, in inhibiting cell activation as well as dermal and pulmonary inflammation and fibrosis in experimental animal models. We used ELISA and fluorescence immunohistochemistry to determine CCL24 levels in serum and CCL24/CCR3 expression in skin biopsies of SSc patients. Skin fibroblasts and endothelial cells treated with CCL24 or SSc serum with or without CM-101 were used to follow cell activation and differentiation. Prevention and treatment in vivo bleomycin (BLM)-induced models were used to evaluate experimental dermal and pulmonary fibrosis progression following treatment with the CM-101 mAb. CCL24 circulating levels were significantly elevated in SSc patients. CCL24/CCR3 expression was strongly increased in SSc skin. Blockade of CCL24 with CM-101 significantly reduced the activation of dermal fibroblasts and their transition to myofibroblasts induced by SSc serum. CM-101 was also able to significantly inhibit endothelial cell activation induced by CCL24. In BLM-induced experimental animal models, CM-101 profoundly inhibited both dermal and pulmonary fibrosis and inflammation. CCL24 plays an important role in pathological processes of skin and lung inflammation and fibrosis. Inhibition of CCL24 by CM-101 mAb can be potentially beneficial for therapeutic use in SSc patients.
Identifiants
pubmed: 31129606
pii: annrheumdis-2019-215119
doi: 10.1136/annrheumdis-2019-215119
pmc: PMC6788878
doi:
Substances chimiques
Antibodies, Monoclonal
0
Chemokine CCL24
0
Polysaccharides, Bacterial
0
streptococcal polysaccharide type III group B
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1260-1268Informations de copyright
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: AM, MSS, AK, NB and VE: ChemomAb employees. JG: ChemomAb consultant. MM-C: ChemomAb consultant, BMS, MSD, Actelion, Sanofi and Biogen.
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