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.