Sirt1 alleviates LPS induced inflammation of periodontal ligament fibroblasts via downregulation of TLR4

Li, Kexin; Lv, Guihao; Pan, Lingfeng

doi:10.1016/j.ijbiomac.2018.07.099

Cited by 44 publications

(35 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a murine model of allergic rhinitis, SIRT1 was shown to reduce TLR4 signaling . Overexpression of SIRT1 in LPS‐exposed periodontal ligament fibroblasts downregulated TLR4, along with reduced levels of the proinflammatory cytokines TNFα, IL‐1α, IL‐6, and IL‐8 . Although the body of direct evidence for TLR4 inhibition by SIRT1 is still very limited, this relationship is highly suggestive, also because numerous other studies not discussed here in detail had shown negative correlations between SIRT1 and TLR4.…”

Section: Downstream Factors Of Melatonin's Actions With Relevance To mentioning

confidence: 58%

Melatonin and inflammation—Story of a double‐edged blade

Hardeland

2018

Journal of Pineal Research

360

350

View full text Add to dashboard Cite

Melatonin is an immune modulator that displays both pro‐ and anti‐inflammatory properties. Proinflammatory actions, which are well documented by many studies in isolated cells or leukocyte‐derived cell lines, can be assumed to enhance the resistance against pathogens. However, they can be detrimental in autoimmune diseases. Anti‐inflammatory actions are of particular medicinal interest, because they are observed in high‐grade inflammation such as sepsis, ischemia/reperfusion, and brain injury, and also in low‐grade inflammation during aging and in neurodegenerative diseases. The mechanisms contributing to anti‐inflammatory effects are manifold and comprise various pathways of secondary signaling. These include numerous antioxidant effects, downregulation of inducible and inhibition of neuronal NO synthases, downregulation of cyclooxygenase‐2, inhibition of high‐mobility group box‐1 signaling and toll‐like receptor‐4 activation, prevention of inflammasome NLRP3 activation, inhibition of NF‐κB activation and upregulation of nuclear factor erythroid 2‐related factor 2 (Nrf2). These effects are also reflected by downregulation of proinflammatory and upregulation of anti‐inflammatory cytokines. Proinflammatory actions of amyloid‐β peptides are reduced by enhancing α‐secretase and inhibition of β‐ and γ‐secretases. A particular role in melatonin's actions seems to be associated with the upregulation of sirtuin‐1 (SIRT1), which shares various effects known from melatonin and additionally interferes with the signaling by the mechanistic target of rapamycin (mTOR) and Notch, and reduces the expression of the proinflammatory lncRNA‐CCL2. The conclusion on a partial mediation by SIRT1 is supported by repeatedly observed inhibitions of melatonin effects by sirtuin inhibitors or knockdown.

show abstract

Section: Downstream Factors Of Melatonin's Actions With Relevance To mentioning

confidence: 58%

Melatonin and inflammation—Story of a double‐edged blade

Hardeland

2018

Journal of Pineal Research

360

350

View full text Add to dashboard Cite

show abstract

“…After activation, TLRs exhibit the key effect of a strong defense against invasive pathogens. LPS may induce TLR4 to activate the downstream NFκB signaling pathway, which can elicit cytokine production and the expressions of various inflammation-relevant genes [16,27,28]. In the present study, LPS could activate the TLR4 signaling pathway, whereas SIRT1 overexpression exhibited Here, k562 cells were subjected to 5 μM of NAC and 10 μg/ mL of LPS for 4 h. a ROS production in k562 cells was reflected by DCF fluorescence intensity.…”

Section: Discussionmentioning

confidence: 68%

“…TLRs play an essential roles in nonspecific immunity, identify numerous exogenetic PAMPs and pathogens and initiate endogenic immune reactions [25,26]. TLR4, a downstream MAPK signal activator and PRR-binding protein, is reportedly inactivated by SIRT1 overexpression [27]. Simultaneously, its downstream NFκB pathway in SIRT6-overexpressing cells is likewise inhibited [28].…”

Section: Discussionmentioning

confidence: 99%

Sirtuin 1 inhibits lipopolysaccharide-induced inflammation in chronic myelogenous leukemia k562 cells through interacting with the Toll-like receptor 4-nuclear factor κ B-reactive oxygen species signaling axis

Wang

Dou

et al. 2020

Cancer Cell Int

View full text Add to dashboard Cite

Background: Chronic myelogenous leukemia (CML) is a clonal myeloproliferative neoplasm resulting from BCR-ABLtransformed hematopoietic stem cells. Previous research has implicated multifunctional proinflammatory cytokines in CML development. It has been reported that Sirtuin 1 (SIRT1) as well as ADP-ribosyltransferase and deacetylase may influence CML cell viability and inflammation. Methods:This study was directed toward exploring the SIRT1-involved in the mechanism of lipopolysaccharide (LPS)-triggered inflammation in CML k562 cells. Results:In our study, the LPS-induced inflammation in k562 cells was reflected by increases in levels of diverse inflammatory cytokines, including interleukin (IL)-10, IL-1β, IL-6, interferon-γ, tumor necrosis factor (TNF)-α and TNF-β. LPS also decreased SIRT1 expression and nuclear location in k562 cells. Furthermore, SIRT1 overexpression inhibited the release of the above mentioned cytokines in LPS-treated cells. We also determined that LPS stimulation could activate Toll-like receptor 4 (TLR4), the nuclear factor κ B (NFκB) subunit, and p65 and produce reactive oxygen species (ROS) in k562 cells. Nevertheless, SIRT1 overexpression decreased TLR4 expression, thereby repressing the phosphorylation of the NFκB subunit and p65 and decreasing ROS production. Conclusions:These findings suggest that SIRT1 is a latent therapeutic target for mitigating LPS-induced inflammation via the TLR4-NFκB-ROS signaling axis.

show abstract

“…In addition to the inhibition of TLR4 activity, a concomitant reduction of TRIF activity or expression level by melatonin was also described . It should be briefly mentioned that SIRT1, which seems to mediate several effects of melatonin, has also been shown to inhibit the TLR4 pathway . This relationship implicates another connection via the TLR4‐binding protein HMGB1 (high mobility group box‐1), which is deacetylated by SIRT1, decreased in its expression, nucleocytoplasmic transfer and release .…”

Section: Mechanisms Whereby Melatonin Regulates Macrophage Polarizationmentioning

confidence: 95%

“…145,146 It should be briefly mentioned that SIRT1, which seems to mediate several effects of melatonin, 16 has also been shown to inhibit the TLR4 pathway. 147,148 This relationship implicates another connection via the TLR4-binding protein HMGB1 (high mobility group box-1), which is deacetylated by SIRT1, decreased in its expression, nucleocytoplasmic transfer and release. 149 The actions of melatonin finally reduce the expression of M1 marker genes, thereby inhibiting M1 macrophage polarization ( Figure 1A).…”

Section: Melatonin Shapes Macrophage Polarization Through Cellular mentioning

confidence: 99%

Melatonin in macrophage biology: Current understanding and future perspectives

Xia

Chen

Zeng

et al. 2019

Journal of Pineal Research

157

126

View full text Add to dashboard Cite

Melatonin is a ubiquitous hormone found in various organisms and highly affects the function of immune cells. In this review, we summarize the current understanding of the significance of melatonin in macrophage biology and the beneficial effects of melatonin in macrophage‐associated diseases. Enzymes associated with synthesis of melatonin, as well as membrane receptors for melatonin, are found in macrophages. Indeed, melatonin influences the phenotype polarization of macrophages. Mechanistically, the roles of melatonin in macrophages are related to several cellular signaling pathways, such as NF‐κB, STATs, and NLRP3/caspase‐1. Notably, miRNAs (eg, miR‐155/‐34a/‐23a), cellular metabolic pathways (eg, α‐KG, HIF‐1α, and ROS), and mitochondrial dynamics and mitophagy are also involved. Thus, melatonin modulates the development and progression of various macrophage‐associated diseases, such as cancer and rheumatoid arthritis. This review provides a better understanding about the importance of melatonin in macrophage biology and macrophage‐associated diseases.

show abstract

Sirt1 alleviates LPS induced inflammation of periodontal ligament fibroblasts via downregulation of TLR4

Cited by 44 publications

References 36 publications

Melatonin and inflammation—Story of a double‐edged blade

Melatonin and inflammation—Story of a double‐edged blade

Sirtuin 1 inhibits lipopolysaccharide-induced inflammation in chronic myelogenous leukemia k562 cells through interacting with the Toll-like receptor 4-nuclear factor κ B-reactive oxygen species signaling axis

Melatonin in macrophage biology: Current understanding and future perspectives

Contact Info

Product

Resources

About