Matairesinol ameliorates experimental autoimmune uveitis by suppression of IRBP-specific Th17 cells

Abstract

We investigated the effects of matairesinol (MAT) in the experimental autoimmune uveitis (EAU), a classical animal model of uveitis. We found that treatment with MAT could alleviate intraocular inflammation of EAU. Notably, Th17 cells in eyes of EAU mice could be predominantly restrained by MAT. Furthermore, MAT could inhibit Th17 differentiation in vitro. In addition, MAT inhibited the signaling of MAPK and ROR-γt, a pivotal transcription factor for Th17 cell differentiation in vitro and in vivo. Taken together, these results suggested that MAT had immune-suppressive effects on autoimmune inflammation through Th17 cells. 2. Materials and methods 2.1. Mice All procedures involving mice were approved by the Laboratory Animal Care and

Multimodal evaluation of an interphotoreceptor retinoid-binding protein-induced mouse model of experimental autoimmune uveitis

“…1c ). These results were comparable to those of previous studies demonstrating that inflammation peaks 3 weeks after IRBP immunization 22 , 28 .…”

“…551459; BD Biosciences, Franklin Lakes, NJ, USA) was intraperitoneally injected into LysM-GFP neutrophil reporter mice at 3-day intervals (Fig. 4 A) 22 . Additionally, to suppress microglial activation, minocycline (45 ml/kg for induction, 22.5 ml/kg for booster; M9511-100MG, Sigma-Aldrich) was intraperitoneally injected into Cx3cr1-GFP microglial reporter mice at 3-day intervals (Fig.…”

Lignans as Pharmacological Agents in Disorders Related to Oxidative Stress and Inflammation: Chemical Synthesis Approaches and Biological Activities

“…Matairesinol suppressed mitochondrial ROS generation and decreased hypoxia-inducible factor-1α (HIF-1α) in hypoxic HeLa cells, inhibited proliferation of human umbilical vein endothelial cells [ 92 ]. In another study, matairesinol in vitro inhibited Th17 cell differentiation via MAPK/ROR-γt signaling pathway and in vivo restrained an interphotoreceptor retinoid-binding protein-specific Th17 proliferation, infiltration and cytokine production, alleviated intraocular inflammation in the eye in the model of experimental autoimmune uveitis [ 192 ]. In rat sepsis model by CLP and the model of LPS-induced neuronal damage, matairesinol exerted neuronal protection, anti-inflammatory and anti-oxidative stress effects by upregulating AMPK and Nrf2/HO-1 pathways and inactivating the MAPK and NF-κB pathways, thereby ameliorating sepsis-mediated brain injury [ 93 ].…”

Cytotoxicity and Antitumor Action of Lignans and Neolignans

“…Matairesinol (MT) was isolated from Juniperus oblonga and exhibited antiinflammatory [74] and cytotoxic activity against neuroblastoma cell lines, with and without tetracycline-inducible MYCN over-expression, and induced apoptosis and cell cycle arrest [39]. MT ameliorated experimental autoimmune uveitis [75] and showed angiogenic activity in vivo and in vitro. This compound also inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) [76].…”