nsc-74859 and Vitreoretinopathy--Proliferative

Interleukin-6 (IL-6) is elevated in intraocular fluid from eyes with proliferative vitreoretinopathy (PVR), but the exact role of the cytokine is still unclear. We investigated the function and mechanism of IL-6 in retinal pigment epithelium (RPE) cell biology in vitro and in a mouse model in vivo.. After treatment with various concentrations of IL-6, RPE cell proliferation was assessed with cell counting kit-8 (CCK-8) assay, and epithelial-mesenchymal transition (EMT) markers were evaluated using western blotting and immunofluorescent staining. The activation of JAK1/STAT3 signaling was determined with western blotting. Moreover, the effects of blockade of IL-6/JAK1/STAT3 signaling were investigated using pharmacological inhibitor S3I-201. For in vivo studies, the PVR model was induced with intravitreal injection of dispase/collagenase in wild-type and IL-6 knockout mice. The severity of PVR was evaluated with histological analysis. The expression of IL-6, gp130, and EMT markers was assessed with quantitative real-time PCR and western blotting.. These findings indicate that IL-6 promotes PVR by inducing RPE proliferation and EMT via the JAK1/STAT3 signaling pathway. We provided new evidence that therapeutic strategies to block IL-6 may be beneficial for PVR.

Topics: Aminosalicylic Acids; Animals; Benzenesulfonates; Cell Line; Cell Proliferation; Cytokine Receptor gp130; Disease Models, Animal; Epithelial Cells; Epithelial-Mesenchymal Transition; Gene Expression Regulation; Humans; Interleukin-6; Janus Kinase 1; Mice; Mice, Knockout; Phosphorylation; Retinal Pigment Epithelium; Signal Transduction; STAT3 Transcription Factor; Vitreoretinopathy, Proliferative