RESULTS
AZM treatment ameliorates the arthritis phenotype of RA FLSs
We firstly analyzed the effects of AZM on the inflammatory phenotype of RA FLSs. and AZM treatment dose-dependently reduced the levels of IL-6 (Fig. 1A), IL-8 (Fig. 1B), MMP-1 (Fig. 1C) and MMP-3 (Fig. 1D) irrespective of TNF-α or IL-1β stimulation. Furthermore, AZM treatment reduced the migration (Fig. 1E) and invasion (Fig. 1F) of RA FLSs. Similarly, there was a strong reduction in CXCL9 (Fig. 1G) and CXCL10 levels (Fig. 1H) in RA FLSs and migrating leucocytes (Fig. 1I) cultured with AZM. In addition, the production of VEGF (Fig. 1J), as well as the pro-angiogenensis ability (Fig. 1K), also decreased when RA FLSs were exposed to AZM. Thus, these data establish the importance of AZM in suppressing the inflammatory phenotype of RA FLSs.
TNF antagonists are the most widely used biological disease-modifying anti-rheumatic drug in RA (Van Schouwenburg, Rispens, & Wolbink, 2013). However, following consideration of the uncertainty of its therapeutic effects and its high price, it is worthy to explore novel treatment strategy. Importantly, AZM reduced the inflammatory factors above as effectively as Etanercept. However, no additive effects were observed when AZM and Etanercept were introduced simultaneously (online Supplementary Fig. 1). Besides, consistent with previous study demonstrating that azithromycin alters macrophage phenotype, in this study, we further confirmed that AZM treatment decreased the production of IL-6, IL-8, TNF-α,IL-1α and IL-1β in PBMC from RA patients (online Supplementary Fig. 2). Therefore, more details would be needed to further support its potential as novel treatment drug for RA.