Salmeterol, a Long‐Acting β2‐Adrenergic Receptor Agonist, Inhibits Macrophage Activation by Lipopolysaccharide From <i>Porphyromonas gingivalis</i>

Sharma, Monika; Patterson, L. Jean; Chapman, Elisha; Flood, Patrick M.

doi:10.1902/jop.2017.160464

Cited by 21 publications

(9 citation statements)

References 46 publications

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“…This suggests that, given the importance of macrophages in inflammatory diseases, the effect of P.g-LPS on macrophage polarization needs to be elucidated. The present study, as previously reported [13,14,36], validated that macrophages underwent M1 phenotypic and functional changes under P.g-LPS stimulation. Interestingly, with the increase of the expression of M1-specific marker and functional molecules, the expression of endogenous PGRN was significantly reduced, suggesting that PGRN is involved in the regulation of M1 polarization under P.g-LPS stimulation.…”

Section: Discussionsupporting

confidence: 90%

“…In this study, we demonstrated that rPGRN inhibited LPS-induced macrophage M1 polarization and these effects were associated with NF-кB and MAPK pathway inhibition. Porphyromonas gingivalis is the main pathogen bacteria of periodontitis and P.g-LPS plays a key role in mediating differentiation and function of M1 macrophages [13,36,37] and in periodontal tissue breakdown [2]. However, other report demonstrate that exposure to P.g-LPS results in diminished pro-inflammatory cytokine production [38].…”

Section: Discussionmentioning

confidence: 99%

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Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways

et al. 2020

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Background: Macrophage M1 polarization plays a pivotal role in inflammatory diseases. Progranulin (PGRN) has potential anti-inflammation action, however, the effect of PGRN on macrophage M1 polarization has been poorly studied. Our study aimed to investigate the effect of PGRN on lipopolysaccharide (LPS)-induced macrophage M1 polarization and clarify the underlying mechanisms. Methods: RAW264.7 cells were polarized to M1 macrophage by LPS with or without recombinant PGRN (rPGRN) and tumor necrosis factor alpha antibody (anti-TNF-α). A cell counting kit-8 assay (CCK-8), flow cytometry, Quantitative Real-Time PCR assay (q-PCR), Western blot assay and enzyme-linked immunosorbent assay (ELISA) were used to determine the effect of different treatments on cell proliferation, expression of surface phenotype marker and expressions and secretion of inflammatory cytokines. The activation of NF-κB/mitogen-activated protein kinase (MAPK) pathways and the nuclear translocation of NF-κB p65 were detected by Western blot and immunofluorescence respectively. THP-1 and primary bone marrow-derived monocytes (BMDMs) were also used to demonstrate effect of PGRN on expressions and secretion of inflammatory cytokines induced by LPS. Results: In RAW264.7 cells, rPGRN at concentrations below 80 ng/ml significantly promoted cell proliferation in dose dependent fashion. rPGRN significantly inhibited LPS-induced change of phenotype (CD86/CD206 ratio) and function (tumor necrosis factor (TNF-α) and inducible nitric oxide synthase (iNOS) expressions). LPS-stimulated secretion of TNF-α and activated phosphorylation of IKKα/β, IкBα, p65, JNK and p38 and the nucleus translocation of NF-кB p65 were also significantly downregulated by rPGRN. In addition, recombinant TNF-α (rTNF-α) significantly boosted TNF-α and iNOS expression vs the control group. Moreover, anti-TNF-α significantly inhibited LPS-induced TNF-α and iNOS expression. In THP-1 and BMDM cells, reversing effect of rPGRN on LPS-enhanced expressions of TNF-α and iNOS and secretion of TNF-α was further demonstrated.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways

et al. 2020

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“…In the treatment of periodontitis, teeth can be cleaned by scaling, root planing, and/or open‐flap surgery, but the activated macrophages involved in the gingival tissue can continue to secrete various cytokines to expand the inflammatory loop (Deo & Bhongade, ). Therefore, polypharmaceutical approaches are necessary to control periodontal disease through both tooth cleaning and immunoregulation, such as the regulation of macrophage polarization and its associated inflammation and tissue destruction (Sharma, Patterson, Chapman, & Flood, ; Yu et al, ).…”

Section: Discussionmentioning

confidence: 99%

Macrophage polarization in human gingival tissue in response to periodontal disease

et al. 2018

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Objective Although accumulating evidence indicates that macrophages are central players in the destructive and reparative phases of periodontal disease, their polarization states at different stages of periodontal inflammation remain unclear. Methods We collected gingival biopsies from patients with chronic periodontitis (P group), gingivitis (G group), or periodontally healthy individuals (H group). Polarized macrophages were identified through immunofluorescence. M1‐ and M2‐related cytokines were detected by immunohistochemistry. Results Compared with the H group, the P group had more M1 cells (higher M1/M2 ratio) and significantly higher TNF‐α, IFN‐γ, IL‐6, and IL‐12 levels. Although the G group also exhibited higher TNF‐α and IL‐12 levels than the H group, they had similar M1/M2 ratios. The M1/M2 ratio and IFN‐γ and IL‐6 levels were significantly higher in the P than the G group. Among M2‐related cytokines, IL‐4 levels were significantly higher in the G than the H group. The M1/M2 ratio was positively correlated with clinical probing depth (PD), and both were positively correlated with IFN‐γ and IL‐6. PD was negatively correlated with IL‐4. Conclusion Macrophage polarization in gingival tissue may be responsible for the development and progression of inflammation‐induced tissue destruction, and modulating macrophage function may be a potential strategy for periodontal disease management.

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“…To test this, we used murine macrophages stimulated with LPS from Porphyromonas gingivalis (PgLPS), an oral pathogen as an in vitro model for the periodontal disease. We have found that Salmeterol shows similar anti-inflammatory effects on PgLPS-stimulated macrophages [115]. Additionally, Feng et al have also shown neuroprotective effects of β-arrestin2 via endogenous opioid arrest in inflammatory microglial cells [116].…”

Section: Effect Of β2-ar Agonists On Nf-κb Pathwaymentioning

confidence: 53%

Adrenergic Receptors as Pharmacological Targets for Neuroinflammation and Neurodegeneration in Parkinson’s Disease

Sharma¹,

Flood²

2019

Neuroprotection

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Inflammation is a key component of the dopaminergic neurodegeneration seen in progressive Parkinson's disease (PD). The presence of activated glial cells, the participation of innate immune system, increased inflammatory molecules such as cytokines and chemokines, and increased oxidative stress and reactive oxygen species are the main neuroinflammatory characteristics present in progressive PD. Therapeutic targets which suppress pro-inflammatory responses by glial cells (mainly microglia) have been shown to be effective treatments for slowing or eliminating the progressive degeneration of neurons within the substantia nigra. In this chapter, we will detail a specific anti-inflammatory therapy using agonists to β2-adrenergic receptors that have been shown to be effective treatments for models of dopaminergic neurodegeneration and that have had efficacy in patients with progressive PD. We will also detail the possible molecular mechanisms of action of this therapeutic in stopping or reversing inflammation within the CNS.

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Salmeterol, a Long‐Acting β2‐Adrenergic Receptor Agonist, Inhibits Macrophage Activation by Lipopolysaccharide From Porphyromonas gingivalis

Abstract: Salmeterol can significantly inhibit activation of macrophage-mediated inflammation by PgLPS, suggesting that use of salmeterol may be an effective treatment in inhibiting or lessening the inflammatory response mediated through TLR pathway activation.

Cited by 21 publications

References 46 publications

Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways

Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways

Macrophage polarization in human gingival tissue in response to periodontal disease

Adrenergic Receptors as Pharmacological Targets for Neuroinflammation and Neurodegeneration in Parkinson’s Disease

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