Interstitial lung disease associated with
rheumatoid arthritis (RA-ILD) can lead to interstitial
fibrosis and even lung failure as a complication of
rheumatoid arthritis (RA), and there is currently no effective treatment and related basic research. Studies have found that
resveratrol (Res) can improve the progression of RA by regulating autophagy, and increasing evidence supports the connection between autophagy and common
interstitial lung disease (ILD). We explored changes in autophagy levels in fibrotic lungs in RA-ILD and found that the level of autophagy is enhanced in the early stage but inhibited in the late stage. However,
resveratrol treatment improved the level of autophagy and reversed the inhibition of autophagy, and attenuated
fibrosis. We created corresponding cell models that exhibited the same phenotypic changes as animal models; under the effect of
resveratrol, the level of
fibrosis changed accordingly, and the fusion process of lysosomes and autophagosomes in autophagy was liberated from the inhibition state.
Resveratrol effects were reversed by the addition of the late autophagy inhibitor
chloroquine. These results suggest that
resveratrol attenuates
pulmonary fibrosis, increases autophagic flux, and modulates the autophagy-lysosome pathway, and particularly it may work by improving the formation of autophagic lysosomes, which may be an effective treatment for induced RA-ILD.