Neutrophil extracellular traps and extracellular histones potentiate IL-17 inflammation in periodontitis

Kim, Tae Sung; Silva, Lakmali Munasinghage; Theofilou, Vasileios Ionas; Greenwell-Wild, Teresa; Li, Lu; Williams, D.; Ikeuchi, Takao; Brenchley, Laurie; Bugge, Thomas H.; Diaz, Patricia I.; Kaplan, Mariana J.; Carmona-Rivera, Carmelo; Moutsopoulos, Niki M.

doi:10.1084/jem.20221751

Cited by 50 publications

(16 citation statements)

References 58 publications

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“…However, whether MGFs also possess SCC-like potential and participate in the regulation of periodontal homeostasis via taste transduction pathway has yet to be investigated. We first re-analyzed sequence data deposited in the GEO RNA-seq database ( 24 , 25 ). We found that the expression of Tas2r143 was only reported in 2 of the 6 RNA-seq databases, and only one of these databases reported the expression of Gnat3.…”

Section: Discussionmentioning

confidence: 99%

Salicin alleviates periodontitis via Tas2r143/gustducin signaling in fibroblasts

Zhang,

Zhou,

Liu

et al. 2024

Front. Immunol.

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IntroductionCells expressing taste signaling elements in non-gustatory tissues have been described as solitary chemosensory cells (SCCs) or tuft cells. These “taste-like” cells play a critical role in the maintenance of tissue homeostasis. Although the expression of SCC markers and taste signaling constituents has been identified in mouse gingivae, their role in periodontal homeostasis is still unclear. MethodsPublic RNA sequencing datasets were re-analyzed and further validated with RT-PCR/qRT-PCR and immunofluorescent staining to explore the expression of TAS2Rs and downstream signaling constituents in mouse gingival fibroblasts (MGFs). The specific action of salicin on MGFs via Tas2r143 was validated with RNA silence, heterologous expression of taste receptor/Gα-gustducin and calcium imaging. The anti-inflammatory effects of salicin against LPS-induced MGFs were investigated in cell cultures, and were further validated with a ligature-induced periodontitis mouse model using Ga-gustducin-null (Gnat3−/−) mice. ResultsThe expression of Tas2r143, Gnat3, Plcb2, and TrpM5 was detected in MGFs. Moreover, salicin could activate Tas2r143, elicited taste signaling and thus inhibited LPS-induced chemokines expression (CXCL1, CXCL2, and CXCL5) in MGFs. Consistently, salicin-treatment inhibited periodontal bone loss, inflammatory/chemotactic factors expression, and neutrophil infiltration in periodontitis mice, while these effects were abolished in Gnat3−/− mice. DiscussionGingival fibroblasts play a critical role in the maintenance of periodontal homeostasis via “SCC-like” activity. Salicin can activate Tas2r143-mediated bitter taste signaling and thus alleviate periodontitis in mouse, indicating a promising approach to the resolution of periodontal inflammation via stimulating the “SCC-like” function of gingival fibroblasts.

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Section: Discussionmentioning

confidence: 99%

Salicin alleviates periodontitis via Tas2r143/gustducin signaling in fibroblasts

Zhang,

Zhou,

Liu

et al. 2024

Front. Immunol.

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“…This process leads to the enhanced production of both proinflammatory and regulatory cytokines. The cytokines promote further inflammation, leading to further inflammatory damage (secondary injury) to the periodontal tissues (Figure B). , The gingival epithelium prevents bacterial invasion via the continuous shedding and renewal of cells, and the connective tissue in the subgingival sulcus increases the thickness of the keratinized area in the presence of inflammation . The epithelial barrier is broken down, and a new environment is formed due to continued bacterial attacks and uncontrolled gingival inflammation.…”

Section: The Role Of Hydrogel In the Treatment Of Periodontitismentioning

confidence: 99%

Advances in Hydrogels for Periodontitis Treatment

Li,

Wang,

Xiao

et al. 2024

ACS Biomater. Sci. Eng.

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Periodontitis is a common condition characterized by a bacterial infection and the disruption of the body's immune-inflammatory response, which causes damage to the teeth and supporting tissues and eventually results in tooth loss. Current therapy involves the systemic and local administration of antibiotics. However, the existing treatments cannot exert effective, sustained release and maintain an effective therapeutic concentration of the drug at the lesion site. Hydrogels are used to treat periodontitis due to their low cytotoxicity, exceptional water retention capability, and controlled drug release profile. Hydrogels can imitate the extracellular matrix of periodontal cells while offering suitable sites to load antibiotics. This article reviews the utilization of hydrogels for periodontitis therapy based on the pathogenesis and clinical manifestations of the disease. Additionally, the latest therapeutic strategies for smart hydrogels and the main techniques for hydrogel preparation have been discussed. The information will aid in designing and preparing future hydrogels for periodontitis treatment.

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“…Numerous research have indicated that neutrophil extracellular traps (NETs) are composed of chromatin DNA fragments covered with granulated proteins, which are released by neutrophils to ensnare microorganisms. 4 , 5 , 6 , 7 , 8 , 9 , 10 Cancer invasion, evasion, and metastasis have also been associated with the genetic material of NETs (NET‐DNA) in recent research studies. 11 , 12 , 13 , 14 , 15 , 16 Moreover, the importance of CCDC25 expression in NET‐DNA cannot be overstated, as it has been detected in numerous cancer types such as cholangiocarcinoma, gastric cancer, hepatocellular carcinoma, and myeloma.…”

Section: Introductionmentioning

confidence: 99%

Integrated analysis of NET‐DNA receptor CCDC25 in malignant tumors: Pan‐cancer analysis

Cheng,

Yin,

Song

2023

Health Science Reports

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BackgroundPreviously, it was reported that the coiled‐coil domain containing 25 (CCDC25) plays a role in the formation of neutrophil extracellular traps (NETs). This study systematically analyzed the expression profiles of CCDC25 in 30 different types of cancer and one type of blood cancer, acute myeloid leukemia.MethodsThe GTEx and CCLE databases were used to evaluate the distribution of CCDC25 expression in both normal tissue and cancer cell lines. A comparison was performed between normal tissue and tumor tissue to analyze the differential expression of CCDC25. We assessed the impact of CCDC25 on the clinical outlook in the TCGA pan‐cancer data set by analyzing the Kaplan–Meier survival plot and conducting COX regression analysis. Moreover, the association between the expression levels of CCDC25 and the tumor microenvironment in multiple cancers was conducted. Additionally, the investigation also examined the link between CCDC25 and immune neoantigen, tumor mutational burden, microsatellite instability, mismatch repair genes (MMRs), HLA‐related genes, and DNA methyltransferase (DNMT).ResultsCCDC25 was expressed in nearly all of the 31 normal tissues while exhibiting a moderate to low level of expression in cancer cell lines. While abnormal expression was detected in the majority of malignancies, there was no link found between elevated CCDC25 levels and overall survival, disease‐free survival, recurrence‐free survival, and disease‐free interval in the TCGA comprehensive cancer data set. Nevertheless, the expression of CCDC25 exhibited a notable link with the infiltration levels of activated CD4 memory T cells, quiescent mast cells, dendritic cells in an activated state, T cells that assist in follicle development, M2 macrophages, and neutrophils in various tumors.ConclusionsIn most cancers, the results indicate that there is no link between CCDC25 and prognosis. However, CCDC25 can be targeted for therapeutic purposes concerning metastasis and immune infiltration.

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Neutrophil extracellular traps and extracellular histones potentiate IL-17 inflammation in periodontitis

Cited by 50 publications

References 58 publications

Salicin alleviates periodontitis via Tas2r143/gustducin signaling in fibroblasts

Salicin alleviates periodontitis via Tas2r143/gustducin signaling in fibroblasts

Advances in Hydrogels for Periodontitis Treatment

Integrated analysis of NET‐DNA receptor CCDC25 in malignant tumors: Pan‐cancer analysis

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