JAK2-STAT3 signaling pathway mediates thrombin-induced proinflammatory actions of microglia in vitro☆

Huang, Cheng-Fang; Ma, Rong; Sun, Shan; Gui-rong, Wei; Fang, Yuan; Liu, Rengang; Li, Gang

doi:10.1016/j.jneuroim.2008.07.004

Cited by 75 publications

(52 citation statements)

References 53 publications

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“…A previous study has indicated that JAK2, as the downstream signal of TLR4, plays an essential role in phagocytosis by macrophages [16]. The JAK2-STAT3 pathway is known to cause a pro-inflammatory response in activation of microglial cells [25,26]. Our results showed that co-cultured with LPS (5 ng/ml) and high glucose (35 mmol/L) markedly augmented the activation of primary microglia and the cytokine production, and this effect can be suppressed by pre-treatment with AG490, a specific inhibitor of JAK2 (Fig.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of LPS-Induced Microglial Inflammation Response via TLR4 Under High Glucose Conditions

Zhang

Dong

Zhang

et al. 2015

Cell Physiol Biochem

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Background: Microglia activation mediated by toll-like receptor 4 (TLR4) plays an important role in neuroinflammation and postoperative cognitive dysfunction (POCD). Diabetes mellitus (DM) has been recently suggested as an independent risk factor for POCD. In this study, we investigate the potential exacerbation of the inflammatory response in primary microglia due to high glucose conditions. Methods: Primary microglial cells were exposed to normal glucose (25 mmol/L) and high glucose (35 mmol/L) levels alone or with lipopolyscaccharide (LPS 0, 2, 5, 10 ng/mL). The pro-inflammatory response of the cells was assessed by measuring changes in cytokine levels and the evaluation of associated signaling pathways. Results: Neither high glucose nor low LPS (≤5ng/ml) alone had an effect on TNF-a and IL-6 levels, but the combination of low LPS and high glucose stimulated the inflammatory response. Analyses of the associated signaling pathways demonstrated that high glucose enhanced the LPS-induced microglial activation via the TLR4/JAK2/STAT3 pathway. Conclusion: This study demonstrates that high glucose, one of the key abnormalities characteristic of DM, can augment LPS-induced microglial activation and inflammatory cytokine levels through the TLR4/JAK2/STAT3 pathway, offering new insight into the pathophysiological relationship between DM and POCD.

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Section: Discussionmentioning

confidence: 99%

Enhancement of LPS-Induced Microglial Inflammation Response via TLR4 Under High Glucose Conditions

Zhang

Dong

Zhang

et al. 2015

Cell Physiol Biochem

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show abstract

“…6,16,17) However, limited information is available on mediation of pro-inflammatory proteins, such as iNOS, in brain cells by dsRNA-activated STAT. In this report, we initially demonstrate that STAT1/3 inactivation leads to decreased iNOS expression in dsRNA-stimulated microglia.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Double-Stranded RNA-Induced Inducible Nitric Oxide Synthase Expression by Fraxinellone and Sauchinone in Murine Microglia

Lee

Won

Yoo

et al. 2009

Biological & Pharmaceutical Bulletin

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“…The STAT family is another latent transcription factor important in regulating proinflammatory cytokine expression [36][37][38][39]. Treatment of BV-2 microglial cells with LPS/IFN-γ increased STAT DNA-binding activity (Fig.…”

Section: Effect Of Luteolin On Stat Signalingmentioning

confidence: 99%

Luteolin inhibits cytokine expression in endotoxin/cytokine-stimulated microglia

Kao

Lin

et al. 2011

The Journal of Nutritional Biochemistry

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JAK2-STAT3 signaling pathway mediates thrombin-induced proinflammatory actions of microglia in vitro☆

Cited by 75 publications

References 53 publications

Enhancement of LPS-Induced Microglial Inflammation Response via TLR4 Under High Glucose Conditions

Enhancement of LPS-Induced Microglial Inflammation Response via TLR4 Under High Glucose Conditions

Inhibition of Double-Stranded RNA-Induced Inducible Nitric Oxide Synthase Expression by Fraxinellone and Sauchinone in Murine Microglia

Luteolin inhibits cytokine expression in endotoxin/cytokine-stimulated microglia

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