Immunomodulatory effects of Kaempferol on microglial and Macrophage cells during the progression of diabetic retinopathy.

Autor: Albalawi FE; Regional laboratory, blood bank and poisons centre, Sakaka 72346, Saudi Arabia; Medical College, Fahad Bin Sultan University, Tabuk 47721, Saudi Arabia. Electronic address: Faeialbalawi@moh.gov.sa., Alsharif I; Department of Biology, Jamoum University College, Umm Al-Qura University, 21955, Makkah, Saudi Arabia., Moawadh MS; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia., Alkhoshaiban A; Unit of Scientific Research, Applied College, Qassim University, Saudi Arabia., Falah Alshehri F; Department of Medical Laboratories, College of Applied Medical Sciences, Ad Dawadimi-17464, Shaqra University, Saudi Arabia., Albalawi AE; Faculty of science, Department of Biology, University of Tabuk, Tabuk 47913, Saudi Arabia., Althobaiti NA; Biology Department, College of Science and Humanities, Al Quwaiiyah, Shaqra University, Al Quwaiiyah 19257, Saudi Arabia., Alharbi ZM; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia., Almohaimeed HM; Department of Basic Science, College of Medicine, Princess Nourah bint Abdulrahman University, P.O.Box 84428, Riyadh 11671, Saudi Arabia.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 May 30; Vol. 133, pp. 112021. Date of Electronic Publication: 2024 Apr 15.
DOI: 10.1016/j.intimp.2024.112021
Abstrakt: Background: Diabetic retinopathy (DR) stands as a prevalent secondary complication of diabetes, notably Type 1 Diabetes Mellitus (T1D), characterized by immune system involvement potentially impacting the retinal immune response mediated by microglia. Early stages of DR witness blood-retinal barrier permeabilization, facilitating peripheral immune cell interaction with the retinal immune system. Kaempferol (Kae), known for its potent anti-inflammatory activity, presents a promising avenue in DR treatment by targeting the immune mechanisms underlying its onset and progression. Our investigation delves into the molecular intricacies of innate immune cell interaction during DR progression and the attenuation of inflammatory processes pivotal to its pathology.
Methods: Employing in vitro studies, we exposed HAPI microglial and J774.A1 macrophage cells to pro-inflammatory stimuli in the presence or absence of Kae. Ex vivo and in vivo experiments utilized BB rats, a T1D animal model. Retinal explants from BB rats were cultured with Kae, while intraperitoneal Kae injections were administered to BB rats for 15 days. Quantitative PCR, Western blotting, immunofluorescence, and Spectral Domain - Optical Coherence Tomography (SD-OCT) facilitated survival assessment, cellular signaling analysis, and inflammatory marker determination.
Results: Results demonstrate Kae significantly mitigates inflammatory processes across in vitro, ex vivo, and in vivo DR models, primarily targeting immune cell responses. Kae administration notably inhibits proinflammatory responses during DR progression while promoting an anti-inflammatory milieu, chiefly through microglia-mediated synthesis of Arginase-1 and Hemeoxygenase-1(HO-1). In vivo, Kae administration effectively preserves retinal integrity amid DR progression.
Conclusions: Our findings elucidate the interplay between retinal and systemic immune cells in DR progression, underscoring a differential treatment response predominantly orchestrated by microglia's anti-inflammatory action. Kae treatment induces a phenotypic and functional shift in immune cells, delaying DR progression, thereby spotlighting microglial cells as a promising therapeutic target in DR management.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: