Anti-inflammatory effects of fluoxetine in lipopolysaccharide(LPS)-stimulated microglial cells

Liu, Dexiang; Wang, Zhen; Liu, Shangming; Wang, Fuwu; Zhao, Shidou; Hao, Aijun

doi:10.1016/j.neuropharm.2011.04.033

Cited by 184 publications

(124 citation statements)

References 61 publications

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“…13 It was suggested that fluoxetine inhibits the mRNA for these cytokines (as well as for IL-6) by inhibiting the phosphorylation and nuclear translocation of the p65 subunit of NF-κB, and phosphorylation of p38 mitogen-activated protein kinase (MAPK) in the LPS-stimulated microglia. 14 In experiments with human synovial cells, it was found that fluoxetine causes inhibition of the synthesis of hyaluronic acid, prostaglandin E2, and nitric oxide. 15 IL-10 is a key regulator of depression symptoms and modulates depressive-like behavior.…”

Section: Introductionmentioning

confidence: 99%

Study on anti-inflammatory and immunomodulatory effects of fluoxetine in rat models of inflammation

et al. 2015

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The aim of the present study was to evaluate the anti-inflammatory effect of fluoxetine in carrageenan-and lipoplysaccharideinduced models of inflammation by investigating the changes in serum levels of pro-inflammatory cytokine TNF-α and anti-inflammatory cytokines IL-10 and TGF-β after single and repeated administration of the drug. To study the effect of a single and repeated dose fluoxetine on carrageenan-induced paw edema male Wistar rats were divided into five groups (n = 8): control group; positive control group; and three experimental groups treated with 5, 10, and 20 mg/kg bodyweight (bw) fluoxetine, respectively. To study the effect of a single and repeated dose of fluoxetine on serum cytokine levels, the animals were divided in four groups (n = 8): two control groups treated with saline and two experimental groups treated with fluoxetine 20 mg/kg bw. Carrageenan and LPS were injected immediately after fluoxetine or saline injection. Serum cytokine concentrations were tested by enzyme immunoassay. In single administration only the highest dose used inhibited carrageenan-induced inflammation. Edema inhibition was seen with 10 and 20 mg/kg bw fluoxetine after repeated administration. At 24 h a statistically significant effect on inhibition of carrageenan edema was found only in rats treated with 20 mg/kg bw fluoxetine In carrageenan-induced inflammation, fluoxetine significantly increased Il-10 and decreased TNF-α after repeated administration. Surprisingly, in single-dose treated animals an increase in TNF-α values upon fluoxetine administration was observed in this model of inflammation. In LPS-induced inflammation, fluoxetine significantly decreased TNF-α after single and repeated treatment. Fluoxetine has anti-inflammatory and immunomodulatory effect in the carrageenan-induced model of exudative inflammation. In LPS-induced inflammation it showed an immunomodulatory effect manifested with a decrease in pro-inflammatory cytokine TNF-α.

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Section: Introductionmentioning

confidence: 99%

Study on anti-inflammatory and immunomodulatory effects of fluoxetine in rat models of inflammation

et al. 2015

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“…For example, fluoxetine reduced TNFα and IL-6 levels in microglia stimulated with LPS (Liu et al, 2011), and pretreatment with fluoxetine reduced peripheral cytokines in animal models of inflammatory diseases, such as rheumatoid arthritis, LPS-induced septic shock, and allergic asthma (Abdel-Salam et al, 2004;Roumestan et al, 2007;Sacre et al, 2010). However, the effects of antidepressants on inflammation are controversial, as variable changes, or no changes, in cytokines have been reported in some studies following antidepressant administration, particularly in the serum of depressed patients (reviewed in Baumeister et al, 2015), and anti-inflammatory agents were reported to impair the behavioral responses to antidepressants (Warner-Schmidt et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Stress-induced neuroinflammation is mediated by GSK3-dependent TLR4 signaling that promotes susceptibility to depression-like behavior

Cheng

Jope

Beurel

2016

Psychoneuroendocrinology

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“…Stimulation of TLR4 triggers to activation of transcription factors, which, in turn, enhance the synthesis of inflammatory genes, including cytokines and chemokines (Miller et al 2005). The formation of an LPS-TLR4/MD-2 complex and the subsequent recruitment of MyD88 adaptor protein, induces activation of MAPKs as well as the transcriptional nuclear factor kB, leading in consequence to secretion of various inflammatory mediators (Ryu et al 2000;Medzhitov 2001;Trinchieri and Sher 2007;Liu et al 2011). The MAPK family of proteins includes ERK1/2, SAPK/JNK and p38 (Koistinaho and Koistinaho 2005).…”

Section: R E T R a C T E Dmentioning

confidence: 99%

Retracted: Anti‐inflammatory properties of tianeptine on lipopolysaccharide‐induced changes in microglial cells involve toll‐like receptor‐related pathways

Ślusarczyk

Trojan

Głombik

et al. 2016

Journal of Neurochemistry

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Accumulating evidence suggests that activation of microglia plays a key role in the pathogenesis of depression. Activated microglia produce a wide range of factors whose prolonged or excessive release may lead to brain disorders. Thus, the inhibition of microglial cells may be beneficial in the treatment of depressive diseases. Tianeptine is an atypical antidepressant drug with proven clinical efficacy, but its mechanism of action remains still not fully understood. In the present study, using microglial cultures we investigated whether tianeptine modifies microglial activation after lipopolysaccharide (LPS) stimulation and which intracellular pathways are involved in the activity of this antidepressant. Our study shows that tianeptine attenuated the LPS-evoked inflammatory activation of microglia by decreasing the expression of proinflammatory cytokines such as IL-1b, IL-18, IL-6 and tumor necrosis factor a (TNF-a), the release of nitric oxide (NO) and reactive oxygen species (ROS) as well as the expression of inducible nitric oxide synthase. Analyses of signaling pathways demonstrate that tianeptine led to the suppression of LPS-induced TLR4 expression and ERK1/2 phosphorylation. Furthermore, our study reveals the inhibitory impact of tianeptine on caspase-3-induced PKCd degradation and consequently on the activation of NF-jB factor in microglial cells. Taken together, present results show anti-inflammatory properties of tianeptine in microglial cultures stimulated by LPS. This study provides evidence that the inhibition of microglial activation may underlie the therapeutic activity of tianeptine. Keywords: antidepressant drugs, cytokines, inflammation, intracellular pathways, microglia, tianeptine. J. Neurochem. (2016) 136, 958-970. Increasing evidence indicates that microglia, the resident immune cells in the central nervous system (CNS), may be considered the main mediators of inflammation-associated disorders. These cells manage the innate and adaptive immune responses in various pathological processes including brain trauma, ischemia, stroke and infections, as well as during CNS repair (Graeber and Streit 2010;Yang et al. 2011). It has been observed that active microglia can clear Received September 29, 2015; revised manuscript received November 16, 2015; accepted November 17, 2015. Address correspondence and reprint requests to Agnieszka BastaKaim, Department of Experimental Neuroendocrinology, Polish Academy of Sciences, 12 Sme z tna St., 31-343 Krak ow, Poland. E-mail: basta@if-pan.krakow.plAbbreviations used: AP-1, activator protein-1; CD40, cluster of differentiation 40; DCFH, 2 0 ,7 0 -dichlorodihydrofluorescin; DCFH-DA, 2 0 ,7 0 -dichlorofluorescin diacetate; DMEM, Dulbecco's modified Eagle medium; FAM, fluorescein amidite; FBS, fetal bovine serum; HBSS, Hank's Balanced Salt Solution; HPA, hypothalamus-pituitary-adrenal; IL-18, interleukin 18; IL-1b, interleukin 1b; IL-6, interleukin 6; JNK, cJun N-terminal kinase; LDH, lactate dehydrogenase; MCP-1, monocyte chemoattractant protein-1;...

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Anti-inflammatory effects of fluoxetine in lipopolysaccharide(LPS)-stimulated microglial cells

Cited by 184 publications

References 61 publications

Study on anti-inflammatory and immunomodulatory effects of fluoxetine in rat models of inflammation

Study on anti-inflammatory and immunomodulatory effects of fluoxetine in rat models of inflammation

Stress-induced neuroinflammation is mediated by GSK3-dependent TLR4 signaling that promotes susceptibility to depression-like behavior

Retracted: Anti‐inflammatory properties of tianeptine on lipopolysaccharide‐induced changes in microglial cells involve toll‐like receptor‐related pathways

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