Sodium Phenylbutyrate Ameliorates Inflammatory Response Induced by Staphylococcus aureus Lipoteichoic Acid via Suppressing TLR2/NF-κB/NLRP3 Pathways in MAC-T Cells

Wang, Xin; Zhang, Mengmeng; Jiang, Ning; Zhang, Aizhong

doi:10.3390/molecules23123056

Cited by 11 publications

(8 citation statements)

References 34 publications

(42 reference statements)

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“…The interaction between TLR2 and NLRP3 inflammasome has been also reported in various cell types. In monocytes (42), macrophages (43,44), bone marrow-derived DCs (45) and several different cell lines (46,47), lacking TLR2 failed to upregulate NLRP3 inflammasome as well as its substrate IL-1β. Therefore, our results have suggested that activation of NLRP3 inflammasome induced by OVA requires TLR2 signaling, thus TLR2 may mediate allergic airway inflammation through regulating NLRP3 inflammasome activity.…”

Section: Discussionmentioning

confidence: 99%

TLR2-Melatonin Feedback Loop Regulates the Activation of NLRP3 Inflammasome in Murine Allergic Airway Inflammation

Zhao

Xie

et al. 2020

Front. Immunol.

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Toll-like receptor 2 (TLR2) is suggested to initiate the activation of NLRP3 inflammasome, and considered to be involved in asthma. The findings that melatonin modulates TLRs-mediated immune responses, together with the suppressing effect of TLRs on endogenous melatonin synthesis, support the possibility that a feedback loop exists between TLRs system and endogenous melatonin synthesis. To determine whether TLR2-melatonin feedback loop exists in allergic airway disease and regulates NLRP3 inflammasome activity, wild-type (WT) and TLR2 −/− mice were challenged with OVA to establish allergic airway disease model. Following OVA challenge, WT mice exhibited increased-expression of TLR2, activation of NLRP3 inflammasome and marked airway inflammation, which were all effectively inhibited in the TLR2 −/− mice, indicating that TLR2-NLRP3 mediated airway inflammation. Meanwhile, melatonin biosynthesis was reduced in OVA-challenged WT mice, while such reduction was notably rescued by TLR2 deficiency, suggesting that TLR2-NLRP3-mediated allergic airway inflammation was associated with decreased endogenous melatonin biosynthesis. Furthermore, addition of melatonin to OVA-challenged WT mice pronouncedly ameliorated airway inflammation, decreased TLR2 expression and NLRP3 inflammasome activation, further implying that melatonin in turn inhibited airway inflammation via suppressing TLR2-NLRP3 signal. Most interestingly, although melatonin receptor antagonist luzindole significantly reduced the protein expressions of ASMT, AANAT and subsequent level of melatonin in OVA-challenged TLR2 −/− mice, it exhibited null effect on leukocytes infiltration, Th2-cytokines production and NLRP3 activity. These results indicate that a TLR2-melatonin feedback loop regulates NLRP3 inflammasome activity in allergic airway inflammation, and melatonin may be a promising therapeutic medicine for airway inflammatory diseases such as asthma.

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Section: Discussionmentioning

confidence: 99%

TLR2-Melatonin Feedback Loop Regulates the Activation of NLRP3 Inflammasome in Murine Allergic Airway Inflammation

Zhao

Xie

et al. 2020

Front. Immunol.

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“…On the other hand, many researchers seem to believe that LTA acts as a TLR2 agonist. For example, aLTA inhibits LPS-induced B cell proliferation in vitro, ex vivo, and in vivo models, but the effect was not observed in the splenocytes from TLR2-deficient mice, suggesting that TLR2 is involved in aLTA-mediated signaling [ 30 ]. Two independent studies by Wang and Jiang used sodium phenylbutyrate and matrine, respectively, to inhibit the aLTA-induced TLR2 signaling pathway [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Lipoteichoic Acid from Staphylococcus aureus Activates the Complement System via C3 Induction and CD55 Inhibition

Jung

Kim²,

Jang

et al. 2021

Microorganisms

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Staphylococcus aureus inhibits complement activity by secreting a variety of toxins. However, the underlying mechanism of complement component regulation by lipoteichoic acid (LTA), a cell wall component of S. aureus, has not been elucidated. In this study, we observed that aLTA (LTA of S. aureus) increased C3 expression in THP-1 cells. The mechanism of aLTA-mediated C3 induction includes an aLTA-toll-like receptor (TLR) 2 interaction, interleukin 1 receptor associated kinase (IRAK) 2 recruitment, and nuclear factor kappa B (NF-kB) activation. In HepG2 cells, C3 protein production begins to increase from 3 h and increases steadily until 48 h. On the other hand, CD55 levels increased up to 6 h after aLTA treatment and started to decrease after 24 h and levels were decreased at 48 h by more than 50% compared to untreated cells. The expression of CD55 in HepG2 cells was shown to be regulated by IRAK-M induced by aLTA. Serum C3 levels increased in mice injected with aLTA, which resulted in an increase in the amount and activity of the membrane attack complex (MAC). We also observed that CD55 mRNA was increased in the liver 24 h after aLTA injection, but was decreased 48 h after injection. These results suggest that aLTA increases complement levels via induction of C3 and inhibition of CD55, which may cause associated MAC-mediated liver damage.

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“…How PBA increases the number of dendritic spines of the pyramidal neurons of the PFC, the CA1 subregion of the hippocampus and medium spiny neurons of the NAcc in old mice is not known at the present time. However, several reports have suggested that PBA has anti‐inflammatory and antioxidant properties (Jangra et al., 2017; Wang, Zhang, Jiang, & Zhang, 2018; Zeng et al., 2017). In addition, recent reports also suggest that PBA reduces endoplamasmic reticulum (ER) stress (for review see Khan, Komarya, & Jena, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…A recent report using lipopolysaccharide (LPS) to induce lung inflammation as a specific mice model of acute lung injury suggests that PBA prevents the activation of the NF‐κB pathway, and reduces the release of pro‐inflammatory mediators IL‐1β, TNF‐α, and IL‐6 (Zeng et al., 2017). In addition, another recent study using Staphylococcus aurous lipoteichoic acid‐stimulated mammary alveolar cells suggests that PBA exerts its anti‐inflammatory effect by suppressing the TLR2/NF‐kB/NLRP3 pathway (Wang et al, 2018) and also reported a reduced expression of IL‐1β, TNF‐α, IL‐6, and caspase‐1. Interestingly, a recent report has demonstrated that PBA ameliorated the effects of chronic restraint stress on cognitive functions such as memory, and also increased the BDNF levels and reduced the IL‐1β levels in the PFC and hippocampus and only reduced the TNF‐α levels in the hippocampus and the serum corticosterone levels in the restraint stress animal models (Jangra et al., 2017).…”

Section: Discussionmentioning

confidence: 99%

Phenylbutyrate ameliorates prefrontal cortex, hippocampus, and nucleus accumbens neural atrophy as well as synaptophysin and GFAP stress in aging mice

Carvajal-Flores

Díaz

Flores-Gómez

et al. 2020

Synapse

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Recent reports on brain aging suggest that oxidative stress and inflammatory processes contribute to aging. Interestingly, sodium phenylbutyrate (PBA) is an inhibitor of histone deacetylase, which has anti‐inflammatory properties. Several reports have suggested the effect of PBA on learning and memory processes, however there are no studies of the effect of this inhibitor of histone deacetylase on aging. Consequently, in the present study, the effect of PBA was studied in 18‐month‐old mice. The animals were administered PBA for 2 months after locomotor activity treatment and Morris water maze tests were performed. The Golgi‐Cox staining technique and immunohistochemistry for glial fibrillary acidic protein (GFAP) and synaptophysin were performed for the morphological procedures. The administration of PBA improves learning and memory according to the Morris water maze test compared to vehicle‐treated animals, which had unchanged locomotor activity. Using Golgi‐Cox staining, dendritic length and the number of dendritic spines were measured in limbic regions, such as the nucleus accumbens (NAcc), prefrontal cortex (PFC) layer 3, and the CA1 of the dorsal hippocampus. In addition, PBA increased the number of dendritic spines in the PFC, NAcc, and CA1 subregions of the hippocampus with an increase in dendritic length only in the CA1 region. Moreover, PBA reduced the levels of the GFAP and increased the levels of synaptophysin in the studied regions. Thus, PBA can be a useful pharmacological tool to prevent or delay synaptic plasticity damage and cognitive impairment caused by age.

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Sodium Phenylbutyrate Ameliorates Inflammatory Response Induced by Staphylococcus aureus Lipoteichoic Acid via Suppressing TLR2/NF-κB/NLRP3 Pathways in MAC-T Cells

Cited by 11 publications

References 34 publications

TLR2-Melatonin Feedback Loop Regulates the Activation of NLRP3 Inflammasome in Murine Allergic Airway Inflammation

TLR2-Melatonin Feedback Loop Regulates the Activation of NLRP3 Inflammasome in Murine Allergic Airway Inflammation

Lipoteichoic Acid from Staphylococcus aureus Activates the Complement System via C3 Induction and CD55 Inhibition

Phenylbutyrate ameliorates prefrontal cortex, hippocampus, and nucleus accumbens neural atrophy as well as synaptophysin and GFAP stress in aging mice

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