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Monocytes influenced fibrotic process in systemic sclerosis patients
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The fibrotic process in a subset of patients with systemic sclerosis was influenced by circulating monocytes with elevated levels of versican and the chemokine CCL2, according to study results.
Researchers in Japan studied circulating CR14+ monocytes isolated from 36 patients with systemic sclerosis (SSc; mean age, 55.3 years; 32 women) and 32 healthy controls (mean age, 45.8 years; 16 women). A DNA microarray and semi-quantitative or quantitative polymerase chain reaction assessed the gene expression profiles of the monocytes. Culture supernatants of unstimulated monocytes by immunoblotting or ELISA, and immunocytostaining were used to evaluate protein expression.
Two independent sets of pooled monocyte RNA were obtained from five SSc patients and five healthy controls. Expression levels of the individual genes were compared to identify those that were upregulated in SSc monocytes.
The SSc monocytes upregulated versican and CCL2, according to step-wise approach to profiling gene expression. The enhanced production of versican and CCL2 in SSc monocytes compared with controls’ monocytes was confirmed after analyzing proteins expressed in monocyte culture supernatants.
Researchers said CCL2 was bound to chondroitin sulfate (CS) chains of versican and co-localized with versican in the monocytes’ Golgi apparatus. When binding occurred, CCL2 displayed a greater ability to mediate monocyte migration, which resulted because the binding provided protection from protease attack and the CCL2 gradient formation.
“Circulating monocytes with elevated versican and CCL2 levels may contribute to the fibrotic process in a subset of SSc patients by amplifying a positive feedback loop consisting of versican, CCL2 and the influx of monocytes,” the researchers concluded. “Further studies evaluating the roles of circulating monocytes in the pathogenic process of SSc should help to elucidate the complex pathophysiology of SSC and assist us to develop novel therapeutic strategies in this multisystem fibrotic disease.”
Disclosures: The researchers report no relevant financial disclosures.
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