Enhanced neutrophil autophagy and increased concentrations of IL-6, IL-8, IL-10 and MCP-1 in rheumatoid arthritis.

Abstract:

:Rheumatoid arthritis (RA) is a high morbidity and disability disease with numerous inflammatory cells infiltrating in interstitial of articular cartilages and bones. As the most abundant inflammatory cells, neutrophil has been reported that their apoptosis changed gradually in the circumstance of RA. Apoptosis, one modality of programmed cell death (PCD), is closely associated with autophagy, which indicates neutrophil autophagy may also alter in RA. Flow cytometry, western blotting, immunohistochemistry, immunofluorescence, transmission electron microscope and multiplex antibody microarray were used to comparative investigate the status of neutrophil autophagy in patients with RA and in vitro. The results showed that the expression of autophagy related LC3 protein was up-regulated with lower lysosomal pH in neutrophils from synovial fluid of RA and changed under stimulation of CQ and small RNA interferences (siRNAs) Atg5 transfection, which proved in acute promyelocytic leukemia HL-60 cell lines, predominantly a neutrophilic promyelocyte, treated by plasma and synovial fluid from RA. We further found out the concentration of IL-6, IL-8, IL-10 and MCP-1 was higher in their synovial fluid which may mediate neutrophil autophagy in RA via cytokine-cytokine receptor interaction and IL-17 signaling pathway. Our results indicate that neutrophil autophagy may be a novel perspective to understand the pathology which may provide a new maker to diagnose RA and IL-8, IL-10, MCP-1 specific antagonists and neutrophil autophagy target inhibitors may improve the therapeutic effect of RA someday.

journal_name

Int Immunopharmacol

authors

An Q,Yan W,Zhao Y,Yu K

doi

10.1016/j.intimp.2018.09.011

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

119-128

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(18)30602-7

journal_volume

65

pub_type

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