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Expression of Free Fatty Acids and T...

Al-Hadlaq, Malak Adel,

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Expression of Free Fatty Acids and Their Receptors on Oral Neutrophils in Oral Lichen Planus /

Record Type:	Electronic resources : Monograph/item
Title/Author:	Expression of Free Fatty Acids and Their Receptors on Oral Neutrophils in Oral Lichen Planus // Malak Adel Al-Hadlaq.
Author:	Al-Hadlaq, Malak Adel,
Description:	1 electronic resource (97 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 85-11, Section: B.
Contained By:	Dissertations Abstracts International85-11B.
Subject:	Immunology. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31242299
ISBN:	9798382405742

Expression of Free Fatty Acids and Their Receptors on Oral Neutrophils in Oral Lichen Planus /
Al-Hadlaq, Malak Adel,

Expression of Free Fatty Acids and Their Receptors on Oral Neutrophils in Oral Lichen Planus /Malak Adel Al-Hadlaq. - 1 electronic resource (97 pages)

Source: Dissertations Abstracts International, Volume: 85-11, Section: B.

Objectives: The aim of this project is to assess expression of specialized pro-resolving lipid mediators (SPMs) and inflammation resolution receptors on oral neutrophils (oPMNs) in oral lichen planus (OLP) compared to healthy controls. FFAR2 binds short chain fatty acids, FFAR4 binds long chain fatty acids, ERV1 binds Resolvin E1, and ALX binds Lipoxin A4. We hypothesize that in OLP, there is decreased oPMN surface expression of inflammation resolution receptors and decreased levels of SPMs, reflecting a failure of the distinct process of inflammation resolution, and hence progression from acute to chronic inflammation in the disease pathogenesis. SPMs activate the inflammation resolution pathways and are potential therapeutic options, especially for steroid refractory OLP.Methods: OLP cases and healthy controls were recruited from the oral medicine clinic at Brigham and Women's Hospital and the Harvard School of Dental Medicine. Oral rinse samples were collected for oPMN isolation and lipidomics analysis using liquid chromatography-tandem mass spectrometry. oPMNs were labeled and analyzed by flow cytometry. The number/percentage of cells positive for inflammation resolution receptors, quantities of receptors per cell, and levels of lipid mediators of inflammation were compared using two-sample t-tests. Principle component analysis (PCA) was performed to identify clustering trends in lipid profiles and exploratory biomarker analysis was conducted to identify potential salivary biomarkers for OLP.Results: A total of 27 healthy controls and 17 OLP cases were included. Cases had almost double the number of mean total oPMNs (14x103, p<0.01) and viable (CD16+) oPMNs (8x103, p=0.01). The mean percentage of ERV1+ oPMNs was higher in cases than controls (84% vs. 67%, p<0.01). The mean fluorescent intensity (MFI) for receptors in cases vs controls were: 63x103 vs. 90x103 for ERV1 (p<0.01), 83x103 vs. 66x103 for FFAR2 (p=0.02), 53x103 vs. 36x103 for FFAR4 (p=0.02), and 604x103 vs. 690x103 for ALX (p=0.45). Overall, pro-inflammatory lipid mediators were upregulated while pro-resolving lipid mediators were downregulated in OLP cases compared to controls. PCA identified that the lipid mediator profiles were generally different between the two groups by the distinct clustering of samples. Prostaglandin F2 alpha (PGF2α) and 20-hydroxy leukotriene B4 (LTB4) had significantly higher levels in cases and showed good discriminatory potential as biomarkers for OLP.Conclusion: In OLP, there were more ERV1+ oPMNs, but less expression of ERV1. There is variation in the lipid mediator profiles between cases and controls, with downregulation of pro-resolution mediators in OLP. These findings possibly indicate a failure of inflammation resolution in OLP, and potentially explain acute/symptomatic exacerbations of this chronic condition. Further research is required to support translational studies using topical preparations of SPMs in the management of OLP.

English

ISBN: 9798382405742Subjects--Topical Terms:

611031
Immunology.
Subjects--Index Terms:

Inflammation

Expression of Free Fatty Acids and Their Receptors on Oral Neutrophils in Oral Lichen Planus /
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520 $a Objectives: The aim of this project is to assess expression of specialized pro-resolving lipid mediators (SPMs) and inflammation resolution receptors on oral neutrophils (oPMNs) in oral lichen planus (OLP) compared to healthy controls. FFAR2 binds short chain fatty acids, FFAR4 binds long chain fatty acids, ERV1 binds Resolvin E1, and ALX binds Lipoxin A4. We hypothesize that in OLP, there is decreased oPMN surface expression of inflammation resolution receptors and decreased levels of SPMs, reflecting a failure of the distinct process of inflammation resolution, and hence progression from acute to chronic inflammation in the disease pathogenesis. SPMs activate the inflammation resolution pathways and are potential therapeutic options, especially for steroid refractory OLP.Methods: OLP cases and healthy controls were recruited from the oral medicine clinic at Brigham and Women's Hospital and the Harvard School of Dental Medicine. Oral rinse samples were collected for oPMN isolation and lipidomics analysis using liquid chromatography-tandem mass spectrometry. oPMNs were labeled and analyzed by flow cytometry. The number/percentage of cells positive for inflammation resolution receptors, quantities of receptors per cell, and levels of lipid mediators of inflammation were compared using two-sample t-tests. Principle component analysis (PCA) was performed to identify clustering trends in lipid profiles and exploratory biomarker analysis was conducted to identify potential salivary biomarkers for OLP.Results: A total of 27 healthy controls and 17 OLP cases were included. Cases had almost double the number of mean total oPMNs (14x103, p<0.01) and viable (CD16+) oPMNs (8x103, p=0.01). The mean percentage of ERV1+ oPMNs was higher in cases than controls (84% vs. 67%, p<0.01). The mean fluorescent intensity (MFI) for receptors in cases vs controls were: 63x103 vs. 90x103 for ERV1 (p<0.01), 83x103 vs. 66x103 for FFAR2 (p=0.02), 53x103 vs. 36x103 for FFAR4 (p=0.02), and 604x103 vs. 690x103 for ALX (p=0.45). Overall, pro-inflammatory lipid mediators were upregulated while pro-resolving lipid mediators were downregulated in OLP cases compared to controls. PCA identified that the lipid mediator profiles were generally different between the two groups by the distinct clustering of samples. Prostaglandin F2 alpha (PGF2α) and 20-hydroxy leukotriene B4 (LTB4) had significantly higher levels in cases and showed good discriminatory potential as biomarkers for OLP.Conclusion: In OLP, there were more ERV1+ oPMNs, but less expression of ERV1. There is variation in the lipid mediator profiles between cases and controls, with downregulation of pro-resolution mediators in OLP. These findings possibly indicate a failure of inflammation resolution in OLP, and potentially explain acute/symptomatic exacerbations of this chronic condition. Further research is required to support translational studies using topical preparations of SPMs in the management of OLP.
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