The effectiveness of ruxolitinib and cyclophosphamide combination on T helper 17 and regulatory T cells in rat experimental membranous glomerulonephritis.

Autor: Iranzad R; Faculty of Veterinary, Tabriz Branch, Islamic Azad University, Tabriz, Iran; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Hosseini M; Trauma Research Center, Shahid Rajaee (Emtiaz) Trauma Hospital, Shiraz University of Medical Sciences, Shiraz, Iran., Bagheri M; Gastroenteropatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran., Soltani-Zangbar MS; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran., Pirouzpanah M; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Biglari N; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran., Zolfaghari M; Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran., Khaki A; Department of Pathobiology, Faculty of Veterinary, Tabriz Branch, Islamic Azad University, Tabriz, Iran., Aghebati-Maleki L; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Roshangar L; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Badihi E; Medical Philosophy and History Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Afandideh F; Medical Philosophy and History Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Shahabirad R; Medical Philosophy and History Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Shekarchi AA; Department of Pathology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran., Ahmadian Heris J; Department of Allergy and Clinical Immunology, Pediatric Hospital, Tabriz University of Medical Sciences, Tabriz, Iran., Etemadi J; Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Yousefi M; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: yousefime@tbzmed.ac.ir.
Jazyk: angličtina
Zdroj: Molecular and cellular probes [Mol Cell Probes] 2024 Aug; Vol. 76, pp. 101969. Date of Electronic Publication: 2024 Jul 04.
DOI: 10.1016/j.mcp.2024.101969
Abstrakt: The progression and pathogenesis of membranous glomerulonephritis (MGN) are inextricably linked to chronic inflammation. Despite improving clinical remission rates due to the application of cyclophosphamide (CYC), treatment of MGN still requires further exploration. Ruxolitinib (Ruxo) negatively affects the signaling pathways participating in the production of pro-inflammatory cytokines. Hence, we investigated whether the combination of CYC and Ruxo can modulate inflammation through influencing T helper 17 (Th17) lineages and regulatory T cells (Tregs). Passive Heymann nephritis (PHN), an experimental model of MGN, was induced in a population of rats. Then, the animals were divided into five groups: PHN, CYC-receiving, Ruxo-receiving, CYC-Ruxo-receiving PHN rats, and healthy controls. After 28 days of treatment, biochemistry analysis was performed and splenocytes were isolated for flowcytometry investigation of Th17 cells and Tregs. The correlative transcription factors of the cells, alongside their downstream cytokine gene expressions, were also assessed using real-time PCR. Furthermore, serum cytokine signatures for the lymphocytes were determined through ELISA. The combination of CYC and Ruxo significantly reduced the serum values of urea in rats versus the PHN group (24.62 ± 7.970 vs. 40.60 ± 10.81 mg/dL). In contrast to Treg's activities, the functionality of Th17 cells noticeably increased not only in PHN rats but also in CYC or Ruxo-receiving PHN animals when compared with the control (10.60 ± 2.236, 8.800 ± 1.465, 8.680 ± 1.314 vs. 4.420 ± 1.551 %). However, in comparison to the PHN group, the incidence of Th17 cells notably fell in rats receiving CYC and Ruxo (10.60 ± 2.236 vs. 6.000 ± 1.373 %) in favor of the Treg's percentage (5.020 ± 1.761 vs. 8.980 ± 1.178 %), which was verified by the gene expressions and cytokine productions correlative to these lymphocytes. The combination of CYC and Ruxo was able to decline Th17 cells in favor of Tregs improvement in PHN rats, suggesting an innovative combination therapy in MGN treatment approaches.
Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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