PI3K activity in dendritic cells exerts paradoxical effects during autoimmune inflammation

Datler, Hannes; Vogel, Andrea; Kerndl, Martina; Baumgartinger, Christina; Musiejovsky, Laszlo; Makivic, Nina; Frech, Sophie; Niederreiter, Birgit; Haider, Thomas; Pühringer, Marlene; Brunner, Julia; Sharif, Omar; Schabbauer, Gernot

doi:10.1016/j.molimm.2019.03.015

Cited by 11 publications

(10 citation statements)

References 39 publications

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“…TLR4 signalling activates the microglia by triggering a myeloid differentiation factor 88 (MyD88) or Toll/IL-1 R domain-containing adaptor, inducing the IFN-β (TRIF, also known as ticam1)-dependent signalling pathway, and activating the downstream PI3K/Akt signalling pathway [ 7 , 8 ]. After phosphorylation, PI3K/Akt can further activate NF-κB, thereby causing the initiation of inflammatory cascade reactions, which might cause damage to the tissues [ 9 , 10 ]. Therefore, regulating microglia differentiation and inhibiting inflammatory responses in the CNS are essential in EAE treatment.…”

Section: Introductionmentioning

confidence: 99%

Protecting effect of emodin in experimental autoimmune encephalomyelitis mice by inhibiting microglia activation and inflammation via Myd88/PI3K/Akt/NF-κB signalling pathway

Zheng

et al. 2022

Bioengineered

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Experimental autoimmune encephalomyelitis (EAE) is characterized by demyelination of the central nervous system. Emodin is an anthraquinone derivative with comprehensive anti-inflammatory, anti-cancer, and immunomodulatory effects and is widely used in the treatment of inflammatory, tumor, and immune system diseases. However, none of the clinical or experimental studies have explored the therapeutic efficacy of emodin in EAE/multiple sclerosis (MS). Thus, we evaluated the protective effect of emodin on EAE mediated via inhibition of microglia activation and inflammation. Wild-type mice were randomly divided into the normal control, EAE, low-dose emodin, and high-dose emodin groups. Clinical scores and pathological changes were assessed 21 days after immunization. The network pharmacology approach was used to elucidate the underlying mechanisms by using an online database. Molecular docking, polymerase-chain reaction tests, western blotting, and immunofluorescence were performed to verify the network pharmacology results. An in vivo experiment showed that high-dose emodin ameliorated clinical symptoms, inflammatory cell infiltration, and myelination. Pharmacological network analysis showed AKT1 was the main target and that emodin played a key role in MS treatment mainly via the PI3K–Akt pathway. Molecular docking showed that emodin bound well with PI3K, AKT1, and NFKB1. Emodin decreased the expression of phosphorylated(p)-PI3K, p-Akt, NF-κB, and myeloid differentiation factor 88 and the levels of markers (CD86 and CD206) in M1- and M2-phenotype microglia in EAE. Thus, the emodin inhibited microglial activation and exhibited anti-inflammatory and neuroprotective effects against EAE via the Myd88/PI3K/Akt/NF-κB signalling pathway. In conclusion, emodin has a promising role in EAE/MS treatment, warranting further detailed studies.

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Section: Introductionmentioning

confidence: 99%

Protecting effect of emodin in experimental autoimmune encephalomyelitis mice by inhibiting microglia activation and inflammation via Myd88/PI3K/Akt/NF-κB signalling pathway

Zheng

et al. 2022

Bioengineered

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“…Pi3K signalling plays an important role in various cellular processes such as proliferation, migration or antigen presentation. In addition, Pi3K signalling is involved in the pathogenesis of autoimmune diseases and immunity against cancer (20,21). The inhibition of Akt phosphorylation in bone-marrow derived DCs (BMDC) by IL-10 suppresses IKK/NF-κB activation (22,23).…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity of adherent and non‑adherent JAWS II dendritic cells

Maruszewska-Cheruiyot

Machcińska

Kierasińska

et al. 2023

Oncol Lett

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Dendritic cells (DCs) are crucial in the development of immune responses. DC JAWS II is a murine cell line frequently used in DC studies. These cells are grown in two cell fractions: Adherent and non-adherent. The present study aimed to compare these two fractions in both immature and lipopolysaccharide (LPS)-activated JAWS II cells. The present study analysed the condition, phenotype, antigen uptake capability, signalling properties and the influence on the activity of T cells using flow cytometry, mixed cell reaction and ELISA methods. Adherent immature JAWS II cells exhibited increased endocytosis and decreased activation of the Pi3K signalling pathway. After LPS activation, adherent JAWS II cells exhibited increased expression levels of CD80 and CD86 costimulatory molecules, increased endocytosis and an elevated ability to induce T cell proliferation, compared with non-adherent cells. These results demonstrated that the two fractions of JAWS II adherent and non-adherent cells exhibited different properties and this should be taken into account in the planning of research.

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“…There are studies investigating the effects of TPPU, a selective sEH inhibitor (52)(53)(54)(55)(56)(57)(58)(59) on the expression and/or activity of sEH, PI3K, Akt, ERK1/2, CREB, and Bcl-2 under in vitro and in vivo models of various pathological conditions (53)(54)(55)(56). In addition, GPR75, FLC, PI3K, Akt, MAPK, ERK1/2, and CREB have been reported to contribute to the pathogenesis of MS (19,25,(29)(30)(31)(32)(34)(35)(36)(37)(38)(39)(40)(41)57,58). Data from a study in which we previously investigated the effect of sEH inhibition on pro-inflammatory and anti-inflammatory pathways in chronic EAE induced by MOG 35-55 peptide/PT in mice (4) demonstrated that the protective effects of TPPU against EAE-induced inflammation were also associated with increased expression of PPARα/β/ and NLRC3 proteins, as well as decreased expression of TLR4, MyD88, NF-κB p65, p-NF-κB p65, iNOS/neuronal NOS, COX-2, NLRC4, ASC, caspase-1 p20, IL-1β, caspase-11 p20, NOX subunits (gp91 phox ; a superoxide generating NOX enzyme, and p47 phox ; organizer subunit of gp91 phox ), and nitrotyrosine proteins in the brain and spinal cord tissues as compared with the control groups.…”

Section: Discussionmentioning

confidence: 99%

Pro-inflammatory GPR75 and anti-apoptotic phospholipase signaling pathways contribute to the ameliorating effect of soluble epoxide hydrolase inhibition on chronic experimental autoimmune encephalomyelitis in mice

Mehmet Furkan Horat,

Sefika Pinar Senol,

Omer Bahceli

et al. 2023

Cell Mol Biol (Noisy-le-grand)

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PI3K activity in dendritic cells exerts paradoxical effects during autoimmune inflammation

Cited by 11 publications

References 39 publications

Protecting effect of emodin in experimental autoimmune encephalomyelitis mice by inhibiting microglia activation and inflammation via Myd88/PI3K/Akt/NF-κB signalling pathway

Protecting effect of emodin in experimental autoimmune encephalomyelitis mice by inhibiting microglia activation and inflammation via Myd88/PI3K/Akt/NF-κB signalling pathway

Heterogeneity of adherent and non‑adherent JAWS II dendritic cells

Pro-inflammatory GPR75 and anti-apoptotic phospholipase signaling pathways contribute to the ameliorating effect of soluble epoxide hydrolase inhibition on chronic experimental autoimmune encephalomyelitis in mice

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