resolvin-d1 and Keratitis

To investigate the role of lipid mediator, resolvin D1 (RvD1), in corneal inflammation.. The anti-inflammatory effect of RvD1 on stimulated human corneal epithelial cells (HCECs) was assessed. C57BL/6 mice corneas were abraded and treated with RvD1 after stimulation with. RvD1 significantly inhibited cytokine production in HCECs and mouse corneas, cervical DLNs, and spleens while stimulating interleukin-10 (IL-10) production. Corneal opacity development, thickening, and neutrophil infiltration significantly reduced in response to RvD1 stimulation in the. RvD1 inhibited

Topics: Animals; Anti-Inflammatory Agents; Cytokines; Humans; Inflammation; Keratitis; Mice; Mice, Inbred C57BL; Staphylococcus aureus

Here, we explored the protective effects of resolvin D1 (RvD1) in Pseudomonas aeruginosa (PA) keratitis.. C57BL/6 (B6) mice were used as an animal model of PA keratitis. Plate counting and clinical scores were used to assess the severity of the infection and the therapeutic effects of RvD1 in the model. Myeloperoxidase assay was used to detect neutrophil infiltration and activity. Quantitative PCR (qPCR) was used to examine the expression of proflammatory and anti-inflammatory mediators. Immunofluorescence staining and qPCR were performed to identify macrophage polarization.. RvD1 treatment alleviated PA keratitis severity by decreasing corneal bacterial load and inhibiting neutrophil infiltration in the mouse model. Furthermore, RvD1 treatment decreased mRNA levels of TNF-α, IFN-γ, IL-1β, CXCL1, and S100A8/9 while increasing those of IL-1RA, IL-10, and TGF-β1. RvD1 treatment also reduced the aggregation of M1 macrophages and increased that of M2 macrophages. RvD1 provided an auxiliary effect in gatifloxacin-treated mice with PA keratitis.. Based on these findings, RvD1 may improve the prognosis of PA keratitis by inhibiting neutrophil recruitment and activity, dampening the inflammatory response, and promoting M2 macrophage polarization. Thus, RvD1 may be a potential complementary therapy for PA keratitis.

Topics: Animals; Docosahexaenoic Acids; Keratitis; Mice; Mice, Inbred C57BL; Pseudomonas aeruginosa; Pseudomonas Infections

To investigate the effect of Aspirin Triggered-Resolvin D1 (AT-RvD1) as an anti-pyroptosis and anti-inflammatory agent on lipopolysaccharide (LPS) induced acute keratitis in Wistar rats.. Acute keratitis in rats were induced by LPS stromal injection. Inflammatory reaction was measured by clinical score and histological observations. The non-canonical pyroptosis, the role of AT-RvD1 and Docosahexaenoic Acid (DHA) on non-canonical pyroptosis, were verified by quantification real-time PCR (qRT-PCR) and Western-blot. Besides, Human corneal epithelial cells (HCECs) primed with LPS, were stimulated with Nigericin, AT-RvD1 and necrosulfonamide (NSA), a Gasdermin-D (GSDMD) inhibitor separately. CCK-8 tests and flow cytometry were conducted to evaluate the cell viability and death ratio. And the marker of non-canonical pyroptosis were verified by Western blot.. AT-RvD1 and DHA both alleviated the inflammation of rat cornea through inhibiting the expression of Caspase-11 and p30 which was triggered by LPS. Meanwhile, the activation of Caspase-4 and p30 were also significantly suppressed by AT-RvD1 in vitro, which is consistent with the results in rats.. The non-canonical pyroptosis signaling pathways played an important role in rats with acute keratitis. In addition, AT-RvD1 can exert as an anti-inflammatory activity by inhibiting the non-canonical pyroptosis. Hence, it may be a promising and safe agent in treating acute keratitis.

Topics: Animals; Anti-Inflammatory Agents; Aspirin; Caspases; Docosahexaenoic Acids; Inflammation; Keratitis; Lipopolysaccharides; Pyroptosis; Rats; Rats, Wistar

The study aims to investigate the role of the lipid mediator resolvin D1 (RvD1) in bacterial keratitis in a murine model.. The effect of RvD1 on Pseudomonas aeruginosa-stimulated human corneal epithelial cells (HCECs) and mouse macrophages and dendritic cells (DCs) was assessed. C57BL/6 mouse corneas were abraded and treated with RvD1 after stimulation with P. aeruginosa, following which cytokine production level in the cornea and drainage lymph nodes was compared with that in controls. Corneal opacity and thickness were assessed using anterior segment photographs, and optical coherence tomography and corneal infiltrates were analyzed using immunohistochemistry for neutrophils.. RvD1 significantly inhibited pro-inflammatory cytokine production in HCECs, mouse macrophages, and DCs. Corneal opacity and corneal thickness were reduced, and the development of corneal infiltrates, specifically neutrophils, was also significantly inhibited by RvD1 in response to stimulation with P. aeruginosa.. RvD1 inhibits P. aeruginosa-induced corneal inflammation. This finding supports a potential therapeutic approach for patients with bacterial keratitis.

Topics: Animals; Corneal Injuries; Corneal Opacity; Cytokines; Docosahexaenoic Acids; Eye Infections, Bacterial; Humans; Keratitis; Mice; Mice, Inbred C57BL; Pseudomonas aeruginosa; Pseudomonas Infections

The aim of this study was to investigate the effects of the lipid mediator Resolvin D1 in experimental keratitis. C57BL/6J mice were injected with lipopolysaccharide (2 µg/eye), and after 24 hours, the corneal damage was assessed. Clinical score was quantified, and corneal inflammatory biomarkers were detected by immunohistochemistry. A robust accumulation of sub-epithelial macrophages and polymorphonuclear leucocytes, chemokine (C-X-C motif) ligand 1 (also known as keratinocyte-derived chemokine), interleukin-10 and promoters of apoptosis was also observed in lipopolysaccharide-treated mice. Formyl peptide receptor 2 corneal expression was also assessed. The corneal stroma treated with lipopolysaccharide was characterized by presence of macrophages of M1-like subtype and immature fibroblastic cells, marked with Ki67, not fully differentiated in fibroblasts. Indeed, the staining of the cornea with anti-vimentin antibodies, a marker of differentiated myofibroblasts, was very faint. Resolvin D1 attenuated all the inflammatory parameters assessed in the present study, except for IL-10. In conclusion, the data presented here seem to be consistent with the hypothesis that Resolvin D1 protected the cornea from the lipopolysaccharide-induced keratitis by acting on several inflammatory components of this damage, pivoted by Formyl peptide receptor 2 (FPR2) activation and macrophages-leucocytes activity.

Topics: Animals; Apoptosis; Connexin 43; Cornea; Corneal Stroma; Disease Models, Animal; Docosahexaenoic Acids; Fibroblasts; Immunohistochemistry; Inflammation; Interleukin-10; Keratitis; Ki-67 Antigen; Leukocytes; Lipopolysaccharides; Macrophages; Male; Mice; Mice, Inbred C57BL; Phenotype; Vimentin