Impaired microRNA processing in neutrophils from rheumatoid arthritis patients confers their pathogenic profile. Modulation by biological therapies
| Autor: | Nuria Barbarroja, Carlos Perez-Sanchez, Chary López-Pedrera, Alejandra M. Patiño-Trives, R. Ortega, Iván Arias de la Rosa, Eduardo Collantes-Estevez, Alejandro Escudero-Contreras, Patricia Ruiz-Limon, M.A. Caracuel, Maria del Carmen Abalos-Aguilera, Jerusalem Calvo-Gutiérrez, Irene Cecchi, Yolanda Jimenez-Gomez, Carmen Torres-Granados |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Chemokine
Neutrophils Inflammation medicine.disease_cause Biological Therapy Humans Tumor Necrosis Factor-alpha Arthritis Rheumatoid MicroRNAs Article Autoimmunity 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Rheumatoid microRNA medicine Synovial fluid 030304 developmental biology 0303 health sciences biology business.industry Arthritis Hematology 030220 oncology & carcinogenesis biology.protein Cancer research Tumor necrosis factor alpha medicine.symptom business Dicer |
| Zdroj: | Haematologica |
| ISSN: | 1592-8721 0390-6078 |
| Popis: | The aim of this study was to investigate the microRNA (miRNA) expression pattern in neutrophils from rheumatoid arthritis (RA) patients and its contribution to their pathogenic profile and to analyze the effect of specific autoantibodies or inflammatory components in the regulation of miRNA in RA neutrophils and its modulation by biological therapies. Neutrophils were isolated from paired peripheral blood (PB) and synovial fluid samples of 40 patients with RA and from PB of 40 healthy donors. A miRNA array was performed using nCounter technology. Neutrophils from healthy donors were treated in vitrowith antibodies to citrullinated protein antigens isolated from RA patients and tumor necrosis factor-a (TNF-a) or interleukin-6. A number of cytokines and chemokines were analyzed. In vitro treatments of RA-neutrophils with tocilizumab or infliximab were carried out. Transfections with pre-miRNA and DICER downregulation experiments were further performed. RA-neutrophils showed a global downregulation of miRNA and genes involved in their biogenesis, alongside with an upregulation of various potential mRNA targets related to migration and inflammation. Decreased levels of miRNA and DICER correlated with autoimmunity, inflammation and disease activity. Citrullinated protein antigens and TNF-a decreased the expression of numerous miRNA and their biogenesis-related genes, increasing their potential mRNA targets. Infliximab reversed those effects. Transfections with pre-miRNA-223, -126 and -148a specifically modulated genes regulating inflammation, survival and migration whereas DICER depletion influenced the inflammatory profile of neutrophils. Taken together RA-neutrophils exhibited a global low abundance of miRNA induced by autoantibodies and inflammatory markers, which potentially contributed to their pathogenic activation. miRNA biogenesis was significantly impaired in RAneutrophils and further associated with a greater downregulation of miRNA mainly related to migration and inflammation in synovial fluid neutrophils. Finally, anti-TNF-a and anti-interleukin-6 receptor treatments can modulate miRNA levels in the neutrophils, minimizing their inflammatory profile. |
| Databáze: | OpenAIRE |
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