The 眼表面 is continuously exposed to various environmental factors, and innate
and adaptive immunity play crucial roles in 眼表面疾病 (OSDs). Previously, we
have reported that the topical application of RCI001 affords excellent 抗炎
and 抗氧化 effects in 干眼症 and 眼部 chemical burn models. In this study,
we examined the inhibitory effects of RCI001 on the Rac1 and NLRP3 炎性体s in
vitro and in vivo. Following RCI001 application to RAW264.7 and Swiss 3T3 cells, we
measured Rac1 activity using a glutathione-S-transferase (GST) pull-down assay and Gprotein
activation assay kit. In addition, we quantified the expression of 炎症
cytokines (interleukin [IL]-1b, IL-6, and tumor necrosis factor [TNF]-a) in
lipopolysaccharide (LPS)-stimulated RAW264.7 cells using ELISA and real-time PCR. In
the mouse 眼部 alkali burn model, RCI001 was administered via 滴眼液 (10 mg/mL,
twice daily) for 5 days, and 1% prednisolone acetate (PDE) 眼科 suspension was
used as a positive control. 角膜 epithelial integrity (on days 0-5) and histological
examinations were performed, and transcript and protein levels of Rac1, NLRP3,
caspase-1, and IL-1b were quantified using real-time PCR and western blotting in
角膜 tissues collected on days 3 and 5. We observed that RCI001 dosedependently
inhibited Rac1 activity and various 炎症细胞因子 in LPSstimulated
murine macrophages. Furthermore, RCI001 restored 角膜上皮
integrity more rapidly than corticosteroid treatment in chemically injured corneas.
Compared to the saline group, activation of Rac1 and the NLRP3 炎性体/IL-1b
axis was suppressed in the RCI001 group, especially during the early phase of the 眼部
alkali burn model. Topical RCI001 suppressed the expression of activated Rac1 and
炎症细胞因子 in vitro and rapidly restored the injured cornea by inhibiting
activation of Rac1 and the NLRP 炎性体/IL-1b axis in vivo. Accordingly, RCI001
could be a promising therapeutic agent for treating OSDs.
https://www.frontiersin.org/articles/10.3389/fimmu.2022.850287/abstract