Saliva initiates the formation of pro-inflammatory macrophages in vitro

Periodontal disease is associated with chronic oxidative stress and inflammation. Caffeic acid phenethyl ester (CAPE), which is a potent inducer of heme oxygenase 1 (HO1), is a central active component of propolis, and the application of propolis improves periodontal status in diabetic patients. Here, primary murine macrophages were exposed to CAPE. Target gene expression was assessed by whole-genome microarray, RT-PCR and Western blotting. The antioxidative and anti-inflammatory activities of CAPE were examined by exposure of the cells to hydrogen peroxide, saliva and periodontal pathogens. The involvement of HO1 was investigated with the HO1 inhibitor tin protoporphyrin (SnPP) and knockout mice for Nrf2, which is a transcription factor for detoxifying enzymes. CAPE increased HO1 and other heat shock proteins in murine macrophages. A p38 MAPK inhibitor and Nrf2 knockout attenuated CAPE-induced HO1 expression in macrophages. CAPE exerted strong antioxidative activity. Additionally, CAPE reduced the inflammatory response to saliva and periodontal pathogens. Blocking HO1 decreased the antioxidative activity and attenuated the anti-inflammatory activity of CAPE. In conclusion, CAPE exerted its antioxidative effects through the Nrf2-mediated HO1 pathway and its anti-inflammatory effects through NF-κB inhibition. However, preclinical models evaluating the use of CAPE in periodontal inflammation are necessary in future studies.

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“…In support of previous data, 37 primary macrophages showed a massive inflammatory response when exposed to human saliva (Fig. 4a).…”

Section: Resultssupporting

confidence: 92%

Caffeic acid phenethyl ester protects against oxidative stress and dampens inflammation via heme oxygenase 1

et al. 2019

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“…As a part of the initial response to the sciatic nerve injury (Chen et al, 2011), pro-inflammatory cytokines were up-regulated during the acute phase typically lasting for a few hours, which can augmentate tissue damage, neuronal and axonal destruction and demyelination close to the injury site (Pourgonabadi et al, 2016). Between 2 and 7 days after injury, anti-inflammatory cytokines of the sub-acute phase start to increase, whereas pro-inflammatory cytokines decrease with the activation of inflammatory cells (Beck et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

The Effects of Epidermal Neural Crest Stem Cells on Local Inflammation Microenvironment in the Defected Sciatic Nerve of Rats

Dongdong

Liu

et al. 2017

Front. Mol. Neurosci.

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Cell-based therapy is a promising strategy for the repair of peripheral nerve injuries (PNIs). epidermal neural crest stems cells (EPI-NCSCs) are thought to be important donor cells for repairing PNI in different animal models. Following PNI, inflammatory response is important to regulate the repair process. However, the effects of EPI-NCSCs on regulation of local inflammation microenviroment have not been investigated extensively. In the present study, these effects were studied by using 10 mm defected sciatic nerve, which was bridged with 15 mm artificial nerve composed of EPI-NCSCs, extracellular matrix (ECM) and poly (lactide-co-glycolide) (PLGA). Then the expression of pro- and anti-inflammatory cytokines, polarization of macrophages, regulation of fibroblasts and shwann cells (SCs) were assessed by western blot, immunohistochemistry, immunofluorescence staining at 1, 3, 7 and 21 days after bridging. The structure and the function of the bridged nerve were determined by observation under light microscope and by examination of right lateral foot retraction time (LFRT), sciatic function index (SFI), gastrocnemius wet weight and electrophysiology at 9 weeks. After bridging with EPI-NCSCs, the expression of anti-inflammatory cytokines (IL-4 and IL-13) was increased, but decreased for pro-inflammatory cytokines (IL-6 and TNF-α) compared to the control bridging, which was consistent with increase of M2 macrophages and decrease of M1 macrophages at 7 days after transplantation. Likewise, myelin-formed SCs were significantly increased, but decreased for the activated fibroblasts in their number at 21 days. The recovery of structure and function of nerve bridged with EPI-NCSCs was significantly superior to that of DMEM. These results indicated that EPI-NCSCs could be able to regulate and provide more suitable inflammation microenvironment for the repair of defected sciatic nerve.

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“…We have shown previously that the secretome of γ-irradiated PBMCs, and in particular the monocyte population, holds a pro-angiogenetic activity as determined in an aortic ring assay [26]. To determine whether this secretome can also promote inflammatory resolution, we have now exposed primary macrophages and RAW264.7 cells to the secretome of γ-irradiated PBMCs and activated TLR-signaling with LPS or saliva to provoke the expression of pro-inflammatory cytokines [39]. We report here that the secretome of γ-irradiated PBMCs corresponding to 1 × 10 7 cells/mL substantially decreased the expression of IL1 and IL6 in primary macrophages (Figure 1 and Figure S1) and RAW264.7 cells ( Figure 2), equally effective after LPS or saliva treatment.…”

Section: Secretome Suppresses Inflammation In Primary Macrophages Andmentioning

confidence: 99%

“…The saliva supernatant was passed through a filter with a pore diameter of 0.2 µm (Diafil PS, DIA-Nielsen GmbH, Düren, Germany). The saliva from the two donors was pooled and frozen stocks were used to provoke the expression of inflammatory cytokines in macrophages [39].…”

Section: Saliva Preparationmentioning

confidence: 99%

Role for Lipids Secreted by Irradiated Peripheral Blood Mononuclear Cells in Inflammatory Resolution in Vitro

Panahipour

Kochergina

Laggner

et al. 2020

IJMS

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Periodontal inflammation is associated with dying cells that potentially release metabolites helping to promote inflammatory resolution. We had shown earlier that the secretome of irradiated, dying peripheral blood mononuclear cells support in vitro angiogenesis. However, the ability of the secretome to promote inflammatory resolution remains unknown. Here, we determined the expression changes of inflammatory cytokines in murine bone marrow macrophages, RAW264.7 cells, and gingival fibroblasts exposed to the secretome obtained from γ-irradiated peripheral blood mononuclear cells in vitro by RT-PCR and immunoassays. Nuclear translocation of p65 was detected by immunofluorescence staining. Phosphorylation of p65 and degradation of IκB was determined by Western blot. The secretome of irradiated peripheral blood mononuclear cells significantly decreased the expression of IL1 and IL6 in primary macrophages and RAW264.7 cells when exposed to LPS or saliva, and of IL1, IL6, and IL8 in gingival fibroblasts when exposed to IL-1β and TNFα. These changes were associated with decreased phosphorylation and nuclear translocation of p65 but not degradation of IκB in macrophages. We also show that the lipid fraction of the secretome lowered the inflammatory response of macrophages exposed to the inflammatory cues. These results demonstrate that the secretome of irradiated peripheral blood mononuclear cells can lower an in vitro simulated inflammatory response, supporting the overall concept that the secretome of dying cells promotes inflammatory resolution.

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Saliva initiates the formation of pro-inflammatory macrophages in vitro

Cited by 27 publications

References 34 publications

Caffeic acid phenethyl ester protects against oxidative stress and dampens inflammation via heme oxygenase 1

Caffeic acid phenethyl ester protects against oxidative stress and dampens inflammation via heme oxygenase 1

The Effects of Epidermal Neural Crest Stem Cells on Local Inflammation Microenvironment in the Defected Sciatic Nerve of Rats

Role for Lipids Secreted by Irradiated Peripheral Blood Mononuclear Cells in Inflammatory Resolution in Vitro

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