Neuritin inhibits astrogliosis to ameliorate diabetic cognitive dysfunction

Zuo, Zhili; Zhou, Hongli; Zhou, Jiyin

doi:10.1530/jme-20-0321

Cited by 9 publications

(3 citation statements)

References 72 publications

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“…The STAT3-dependent IL-17 production was further confirmed by the pretreatment of cells with a small molecule compound stattic, a selective STAT3 inhibitor that inhibits the activation, dimerization, and nuclear translocation of STAT3 by interacting with its SH2 domain ( 56 , 57 ) and represses STAT3 phosphorylation ( 58 ). In the current study, the pretreatment of PBMCs significantly repressed STAT3 phosphorylation at Tyr705 by cryptococcal stimulation in CD4 + T cells and further diminished the IL-17-producing CD4 + T cells and secretory IL-17 in the cell culture supernatant.…”

Section: Discussionmentioning

confidence: 95%

Cryptococcus neoformans Infection Induces IL-17 Production by Promoting STAT3 Phosphorylation in CD4+ T Cells

et al. 2022

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Cryptococcus neoformans infection in the central nervous system is a severe infectious disease with poor outcomes and high mortality. It has been estimated that there are 220,000 new cases each year. Over 90% of C. neoformans meningitis cases were diagnosed in AIDS patients with CD4+ T cell count <100 cells/μl; however, the mechanism of cryptococcal meningitis in patients with normal immune functions remains unclear. IL-17 is a pro-inflammatory cytokine and plays an important role in anti-fungal immunity. Here we report that significantly high levels of IL-17 were predominantly detected in the cerebrospinal fluid of patients with either AIDS- or non-AIDS-associated C. neoformans meningitis but not in patients with tuberculous meningitis or non-neurosyphilis. Antifungal therapy minimized the IL-17 level in the cerebrospinal fluid. An in vitro mechanistic study showed that C. neoformans stimulation of healthy peripheral blood mononuclear cells prompted IL-17 production, and CD4+ T cells were the predominant IL-17-producing cells. IL-17 production by C. neoformans stimulation was STAT3 signaling dependent. Inhibition of STAT3 phosphorylation attenuated the C. neoformans-mediated IL-17 expression. Our data highlighted the significance of CD4+ T cells in antifungal immunity and suggested IL-17 as a diagnostic biomarker of C. neoformans infection and STAT3 as a checkpoint for antifungal targeted therapies.

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Section: Discussionmentioning

confidence: 95%

Cryptococcus neoformans Infection Induces IL-17 Production by Promoting STAT3 Phosphorylation in CD4+ T Cells

et al. 2022

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“…In the central nervous system, this signaling pathway is closely related to brain in ammation and the survival and development of neurons/glial cells [41]. It has been found that JAK2 and STAT3 can regulate synaptic plasticity in hippocampus, which is closely related to learning and memory, and JAK2-STAT3 signaling pathway is involved in cognitive improvement [20][21][22][23].Therefore, more and more attention has been paid to the role of JAK2-STAT3 signaling pathway in central nervous system diseases, including Alzheimer's disease, depression and anxiety disorders. AG490 is a speci c antagonist of JAK2 and one of the PTK inhibitors [33].…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have also found that JAK2-STAT3 signaling pathway is involved in cognitive improvement [20][21][22][23], and JAK2-STAT3 signaling pathway is proposed to play a role in the activation of α 3 -, α 5 -and α 7 -nAChRs [24][25][26][27][28]. There seems a relationship between α 4 β 2 nAChRs and JAK2-STAT3 as well [29,30].…”

Section: Introductionmentioning

confidence: 99%

Nicotine Activating α4β2 Nicotinic Acetylcholine Receptors to Suppress Neuroinflammation via JAK2-STAT3 Signaling Pathway in Ischemic Rats and Inflammatory Cells

et al. 2022

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Nicotine plays a role in inhibiting the in ammatory factors, which contributes to improving cognitive impairment by activating α 4 β 2 nAChRs in ischemic rats, but the underling mechanism has not been fully elucidated. Janus tyrosine kinase 2-signal transducer and activator of transcription 3 (JAK2-STAT3) signaling pathway is involved in cognitive improvement, and there seems a relationship between nAChRs and JAK2-STAT3 as well. This study was designed to investigate the role of JAK2-STAT3 signaling pathway in nicotine-mediated anti-in ammation effect. Nicotine, DHβE (the most potent competitive antagonist of α 4 β 2 nAChRs) and AG490 (a speci c JAK2-STAT3 blocker) were adopted for intervention treatment in ischemic rats and HEK-293T-hα 4 β 2 cells. Morris Water Maze (MWM) test and 2-[18F]-A-85380 PET imaging were performed to detect the cognition and α 4 β 2 nAChRs in ischemic rats. The results demonstrated that nicotine intervention increased the density of α 4 β 2 nAChRs and improved cognitive impairment, but this effect would be blocked by AG490, while receptors were still upregulated.Essentially, when JAK2-STAT3 signaling pathway was blocked, nicotine could only upregulate the expression of α 4 β 2 nAChRs, but not improve the cognitive function. The results were further con rmed by PCR and Western blot analysis. The cell experiments also showed that nicotine could reduce in ammatory factors stimulated by LPS and upregulate the expression of pJAK2 and pSTAT3 in HEK-293T-hα 4 β 2 cells, while AG490 and DHβE reversed nicotine's effect. In summary, our work indicated that JAK2-STAT3 signaling pathway played an important role in nicotine-induced cognitive improvement by up-regulating α 4 β 2 nAChRs in ischemic rats.

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STAT protein family and cardiovascular diseases: overview of pathological mechanisms and therapeutic implications

Babaei,

Sadraei,

Yarahmadi

et al. 2024

Mol Biol Rep

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Neuritin inhibits astrogliosis to ameliorate diabetic cognitive dysfunction

Cited by 9 publications

References 72 publications

Cryptococcus neoformans Infection Induces IL-17 Production by Promoting STAT3 Phosphorylation in CD4+ T Cells

Cryptococcus neoformans Infection Induces IL-17 Production by Promoting STAT3 Phosphorylation in CD4+ T Cells

Nicotine Activating α4β2 Nicotinic Acetylcholine Receptors to Suppress Neuroinflammation via JAK2-STAT3 Signaling Pathway in Ischemic Rats and Inflammatory Cells

STAT protein family and cardiovascular diseases: overview of pathological mechanisms and therapeutic implications

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