scholarly journals Dysregulated Maresin Concentrations in Plasma and Nasal Secretions From Patients With Chronic Rhinosinusitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Issa Beegun ◽  
Duco S. Koenis ◽  
Ghassan Alusi ◽  
Jesmond Dalli
Keyword(s):  
Healthy Volunteers ◽  
Chronic Rhinosinusitis ◽  
Peripheral Blood ◽  
Disease Onset ◽  
Lipid Mediators ◽  
Upper Respiratory Tract ◽  
Activation Markers ◽  
Local Inflammatory Response ◽  
Liquid Chromatography Tandem Mass ◽  
Nasal Secretions

The mechanisms that lead to disease onset and propagation in patients with chronic rhinosinusitis (CRS) are not fully elucidated. Maresins (MaR) are a family of essential fatty acid-derived lipid mediators that play a central role in the regulation of inflammation with several studies demonstrating that these mediators display protective activities in airway inflammation. Therefore, in the present studies we evaluated whether concentrations of these mediators were altered in both peripheral blood and nasal secretions from CRS patients. Herein, we focused on patients with CRS that also develop nasal polyps (CRSwNP), given that therapeutic options for the treatment of these patients are limited. Thereby, insights into disease mechanisms in these patients may help design more effective treatments. For this purpose, we compared maresin concentrations from CRSwNP patients with those found in healthy volunteers or patients with an upper respiratory tract infection (URTI), as a self-resolving inflammatory condition. Using liquid chromatography tandem mass spectrometry, we found that MaR concentrations were significantly decreased in plasma from patients with CRSwNP when compared to healthy volunteers. MaR concentrations were observed to be significantly upregulated in nasal secretions from patients with CRSwNP when compared with both healthy volunteers and URTI subjects. Concentration of these mediators in both plasma and nasal secretions from CRSwNP patients were positively correlated with quality-of-life scores in these patients. Assessment of the concentrations of other pro-resolving and pro-inflammatory lipid mediators (LM) demonstrated that there was a general shift in LM levels in both plasma and nasal secretions from CRSwNP when compared with healthy volunteers and URTI subjects. Of note, incubation of peripheral blood cells from CRSwNP patients with MaR1 downregulated the expression of activation markers on peripheral blood phagocytes, including CD41 and CD62P, markers of platelet-leukocyte heterotypic aggregates. Together these findings demonstrate that both local and systemic LM concentrations, in particularly those of the MaR family, become altered in patients with CRSwNP. They also suggest that therapeutics designed around MaR1 may be useful in regulating the activation of phagocytes in patients with CRSwNP thereby potentially also limiting the local inflammatory response in these patients.

scholarly journals Local Shifts in Inflammatory and Resolving Lipid Mediators in Response to Tendon Overuse

2021 ◽  
Author(s):  
James F. Markworth ◽  
Kristoffer B. Sugg ◽  
Dylan C. Sarver ◽  
Krishna Rao Maddipati ◽  
Susan V. Brooks
Keyword(s):  
Inflammatory Response ◽  
Myeloid Cell ◽  
Lipid Mediators ◽  
Bioactive Metabolites ◽  
Local Inflammatory Response ◽  
Plantaris Tendon ◽  
Post Surgery ◽  
Liquid Chromatography Tandem Mass ◽  
Connective Tissue Remodeling ◽  
Related Pathway

Tendon inflammation has been implicated in both adaptive connective tissue remodeling and overuse-induced tendinopathy. Lipid mediators control the initiation and resolution of inflammation, but their roles within tendon are largely unknown. Here we profiled local shifts in intratendinous lipid mediators via liquid chromatography-tandem mass spectrometry in response to synergist ablation-induced plantaris tendon overuse. Sixty-four individual lipid mediators were detected in homogenates of habitually loaded plantaris tendons from healthy ambulatory rats. This included many bioactive metabolites of the cyclooxygenase (COX), lipoxygenase (LOX), and epoxygenase (CYP) pathways. Synergist ablation induced a robust inflammatory response at day 3 post-surgery characterized by epitenon infiltration of polymorphonuclear leukocytes (PMNs) and macrophages (MΦ), heightened expression of inflammation-related genes, and increased intratendinous concentrations of the pro-inflammatory eicosanoids thromboxane B2 (TXB2) and prostaglandin E2 (PGE2). By day 7, MΦ became the predominant myeloid cell type in tendon and there were further delayed increases in other COX metabolites including PGD2, PGF2α and PGI2. Specialized pro-resolving mediators (SPMs) including protectin D1 (PD1) and resolvin D6 (RvD6), as well as related pathway markers of D-resolvins (17-HDoHE), E-resolvins (18-HEPE) and lipoxins (15-HETE) were also increased locally in response to tendon overuse, as were many anti-inflammatory fatty acid epoxides of the CYP pathway (e.g. EpETrEs). Nevertheless, intratendinous prostaglandins remained markedly increased even following 28 days of tendon overuse together with a lingering MΦ presence. These data reveal a delayed and prolonged local inflammatory response to tendon overuse characterized by an overwhelming predominance of pro-inflammatory eicosanoids and a relative lack of pro-resolving lipid mediators.

Pulmonary function in patients with chronic rhinosinusitis and allergic rhinitis

2014 ◽  
Vol 128 (3) ◽  
pp. 255-262 ◽  
Author(s):  
S Kariya ◽  
M Okano ◽  
T Oto ◽  
T Higaki ◽  
S Makihara ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Lung Function ◽  
Respiratory Tract ◽  
Pulmonary Function ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Immunoglobulin E ◽  
Respiratory Tract Diseases ◽  
Upper Respiratory Tract ◽  
Nasal Secretions

AbstractBackground:A close relationship between upper and lower respiratory tract diseases has been reported. However, little is known about pulmonary function in patients with upper respiratory tract diseases.Methods:Pulmonary function was measured in: 68 patients with chronic rhinosinusitis without nasal polyps, 135 patients with chronic rhinosinusitis with nasal polyps, 89 patients with allergic rhinitis and 100 normal control subjects. The relationships between pulmonary function and clinical parameters were assessed. These parameters included radiographic severity of chronic rhinosinusitis, serum total immunoglobulin E levels, concentrations of cytokines in nasal secretions and exhaled nitric oxide levels.Results:The pulmonary function of patients with chronic rhinosinusitis was significantly affected. The level of interleukin-5 in nasal secretions was significantly correlated with pulmonary function in patients with chronic rhinosinusitis.Conclusion:The findings indicated latent obstructive lung function changes in chronic rhinosinusitis patients. The cytokines in nasal secretions might be related to obstructive lung function changes in chronic rhinosinusitis.

scholarly journals Expression of Transcript Variants of PTGS1 and PTGS2 Genes among Patients with Chronic Rhinosinusitis with Nasal Polyps

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 135
Author(s):  
Wioletta Pietruszewska ◽  
Wojciech Fendler ◽  
Marta Podwysocka ◽  
Adam J. Białas ◽  
Piotr Kuna ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Direct Sequencing ◽  
Adult Patients ◽  
Control Group ◽  
Reliable Test ◽  
Aggressive Disease ◽  
Transcript Variants

To date, there has been no reliable test to identify unfavorable course of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), especially in aspirin intolerant patients. The research aimed to analyze the expression of transcript variants of PTGS1 and PTGS2 genes in the pathobiology of the disease. The study was performed on 409 adult patients: 206 CRSwNP patients including 44 (21.36%) aspirin intolerant patients and 203 healthy volunteers in the control group. Transcript variants of the PTGS1 and PTGS2 genes named as follows: COX1.1 for NM_000962, COX1.2 for NM_080591, COX1.3 for NM_001271165.1, COX1.4 for NM_001271368.1, COX1.5 for NM_001271166.1, COX2.1 for NM_000963.3, COX2.2 for AY_151286 and COX2.3 for BQ_722004 were confirmed using direct sequencing and quantified using targeted qPCR. The coexistence of all examined transcript variants in the study and the control group and significant differences between both were found. In aspirin sensitive patients, the levels of COX1.2, COX1.3, COX1.4 and COX1.5 isoforms were higher compared to aspirin-tolerant patients. The severity of symptoms was bigger in patients with higher expressions of variants: COX1.1 (R with dCt = −0.134; p = 0.0490), COX1.3 (R = −0.1429; p = 0.0400) and COX1.5 (Rs = −0.1499; p = 0.032). The expression of COX1.1 (Rs = −0.098; p = 0.049) and COX1.5 (Rs = −0.141; p = 0.043) isoforms increased with polyposis advancement in endoscopy. With the CT extent of sinuses opacification, COX1.1 isoform also significantly increased (Rs = −0.163; p = 0.020). The isoforms COX1.3, COX1.4, COX1.5 and COX2.1 may promote milder CRSwNP course. On the contrary, the variants COX1.1, COX1.2 and COX2.2 may be involved in a more aggressive disease.

Inflammatory Cell Populations in Peripheral Blood and Airways following Lps Inhalation in Healthy Volunteers

2002 ◽  
Vol 103 (s47) ◽  
pp. 59P-59P
Author(s):  
MI Allenby ◽  
MW Lethbridge ◽  
RI Ketchell ◽  
A Sousa ◽  
FE Woisin ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Peripheral Blood ◽  
Inflammatory Cell ◽  
Cell Populations

Neuron-Specific Enolase in Nasal Secretions as a Novel Biomarker of Olfactory Dysfunction in Chronic Rhinosinusitis

2016 ◽  
Vol 30 (1) ◽  
pp. 65-69 ◽  
Author(s):  
Namjil N. Tsybikov ◽  
Elena V. Egorova ◽  
Boris I. Kuznik ◽  
Elena V. Fefelova ◽  
Eli Magen
Keyword(s):  
Chronic Rhinosinusitis ◽  
Neuron Specific Enolase ◽  
Olfactory Dysfunction ◽  
Nasal Secretions

Abstract 51: Peripheral Regulatory T cells and Th17 Cells Is Associated With Pathogenesis of Moyamoya Disease

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Leihua Weng ◽  
Xiang Chen ◽  
Yun Xu
Keyword(s):  
Healthy Volunteers ◽  
Moyamoya Disease ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Treg Cells ◽  
Peripheral Blood Lymphocytes ◽  
Pathological Process ◽  
Medium Term ◽  
Significant Difference ◽  
And Gender

Background: Despite unclear pathogenesis, previous studies have suggested immune responses may play a pivotal role in the process of Moyamoya disease (MMD), a rare cerebrovascular occlusive disorder. The objective of this study is aimed to explore the change of peripheral Treg/Th17 in MMDpatients and whether the change is associated with pathogenesis of MMD. Methods: In the present study, we collected 26 MMD patients diagnosed by angiography according to the diagnostic criteria of definitive MMD and recruited 32 healthy volunteers. To explore the balance of peripheral Treg/Th17 in MMD patients, lymphocytes in peripheral blood were harvested and flow cytometry was used to measure the percentage of Treg and Th17in CD4+ Tcells, respectively. Meanwhile, relevant cytokines in serum were measured to evaluate the function of Treg and Th17 cells. Results: According to Suzuki’s angiographic staging of moyamoya disease, patients were divided into subgroups of the preliminary-term, medium-term and late-term. Cerebral hemorrhage is thefirstsymptom of onset occuringin half of patients, followed bycerebral ischemia.Our data revealed that both the percentage of Treg and Th17 cells in peripheral blood lymphocytes was increased in MMD patients compared with volunteer group. Meanwhile, the levels of IL-6, IL-10,IL-12, IL-17, TNF-α, VEGF and TGF-β in serum were significantly increased in MMD patients. In this study, the level of HMGB-1, a middle-late period inflammation biomarker, in serum of MMD patients is obviously elevated compared with volunteers. However, the ratio of Treg/Th17 had no significant difference in MMD patients compared to healthy volunteers. Intriguingly, our data revealed that ratio of Treg/Th17 was significantly increased in late-term MMD patients compared with medium-term patients as evidenced by elevated percentage of Treg cells.. In addition, TGF-β level in later-term MMD patients was significantly higher than this in medium-term MMD patients. No difference was observed in the way of onset and gender between two groups. Conclusion: Enhanced peripheral Treg and Th17 in MMD patients suggested that there may be an immunological component in the pathogenesis of MMD. Peripheral Treg may be associated with pathological process of MMD.

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