Arginase Isoform Expression in Chronic Rhinosinusitis

Nitric oxide (NO) has emerged as an important regulator of upper airway inflammation, mainly as part of the local naso-sinusal defense mechanisms. Increased arginase activity can reduce NO levels by decreasing the availability of its precursor, L-arginine. Chronic rhinosinusitis (CRS) has been associated with low levels of nasal nitric oxide (nNO). Thus, the present study investigates the activity of arginase I (ARG1) and II (ARG2) in CRS and its possible involvement in the pathogenesis of this disease. Under endoscopic view, tissue samples of pathologic (n = 36) and normal (n = 29) rhinosinusal mucosa were collected. Arginase I and II mRNA levels were measured using real-time PCR. Our results showed low arginase I activity in all samples. The levels of ARG2 were significantly higher in patients with chronic rhinosinusitis compared to the control group (fold regulation (FR) 2.22 ± 0.42 vs. 1.31 ± 0.21, p = 0.016). Increased ARG2 expression was found in patients with CRS without nasal polyposis (FR 3.14 ± 1.16 vs. 1.31 ± 0.21, p = 0.0175), in non-allergic CRS (FR 2.55 ± 0.52 vs. 1.31 ± 0.21, p = 0.005), and non-asthmatic CRS (FR 2.42 ± 0.57 vs. 1.31 ± 0.21, p = 0.028). These findings suggest that the upregulation of ARG2 may play a role in the pathology of a distinctive phenotype of CRS.

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Nitric oxide synthase-2 (CCTTT)n polymorphism is associated with local gene expression and clinical manifestations in patients with chronic rhinosinusitis

European Journal of Inflammation ◽

10.1177/20587392211052948 ◽

2022 ◽

Vol 20 ◽

pp. 205873922110529

Author(s):

Kota Takemoto ◽

Sachio Takeno ◽

Takashi Ishino ◽

Tsutomu Ueda ◽

Takao Hamamoto ◽

...

Keyword(s):

Nitric Oxide ◽

Chronic Rhinosinusitis ◽

Mrna Level ◽

Clinical Manifestations ◽

Inferior Turbinate ◽

Recurrence Risk ◽

Ethmoid Sinus ◽

Mrna Levels ◽

Repeat Polymorphism ◽

Significant Difference

Introduction Nitric oxide (NO) is synthesized through NO synthase (NOS). The proximal NOS2 gene promoter contains the pentanucleotide CCTTT repeat polymorphism. We examined whether CCTTT repeats are associated with NOS2 expression in the sinonasal tissues and clinical manifestations in patients with chronic rhinosinusitis. Methods Mucosal specimens were obtained from the ethmoid sinus and inferior turbinate of 30 eosinophilic chronic rhinosinusitis (ECRS) and 28 non-ECRS patients. CCTTT repeats were classified into short alleles (S), with less than or equal to 14, and long alleles (L), with more than 14. The subjects were classified into the L/S + L/L and S/S groups. Results In ECRS, the NOS2 mRNA levels of the ethmoid sinus mucosa were significantly higher in the L/S + L/L group than in the S/S group (median, 1.66 and 0.77, respectively). On the ther hand, ECRS patients showed no significant difference in the NOS2 mRNA level of the inferior turbinate between the L/S + L/L group and the S/S group (median, 0.63 and 0.88, respectively). In ECRS, preoperative SNOT-22 were significantly higher in the L/S + L/L group than in the S/S group, whereas the former group showed a lower postoperative recurrence risk. Conclusion CCTTT repeat polymorphism in the NOS2 promotor gene may be a useful indicator to evaluate ECRS severity and prognosis.

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Predictive and Diagnostic Value of Nasal Nitric Oxide in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps

International Archives of Allergy and Immunology ◽

10.1159/000509211 ◽

2020 ◽

Vol 181 (11) ◽

pp. 853-861

Author(s):

Hao Lv ◽

Pei-Qiang Liu ◽

Rong Xiang ◽

Wei Zhang ◽

Shi-Ming Chen ◽

...

Keyword(s):

Nitric Oxide ◽

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Upper Airway ◽

Central China ◽

Clinical Parameters ◽

Total Ige ◽

Nasal Nitric Oxide ◽

Eosinophilic Chronic Rhinosinusitis ◽

Plasma Cytokines

Background: A hallmark of eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) is mucosal eosinophil-predominant inflammation. Nasal nitric oxide (nNO) is a known biomarker of eosinophilic inflammation in the upper airway. However, the utility of nNO measurement in the upper airway remains controversial. The present study aimed to compare the use of other clinical parameters with nNO to prediagnose patients with eCRSwNP from Central China. Methods: From June 2019 to December 2019, 70 patients with CRSwNP undergoing endoscopic sinus surgery and 30 healthy subjects were enrolled. nNO measurements were performed in all of these subjects. Computed tomography scans, full blood count with differential analysis, and determination of total immunoglobulin E (total IgE) and plasma cytokines were performed before surgery. Receiver operating characteristic curves and logistic regression analysis were used to assess the predictive potential of the clinical parameters. Results: We recruited 24 patients with eCRSwNP and 46 with noneosinophilic CRSwNP (non-eCRSwNP). In patients with eCRSwNP, nNO levels were significantly higher than those in patients with non-eCRSwNP (p < 0.0001). Blood eosinophil percentages and counts, total IgE, and CT-derived ethmoid sinus and maxillary sinus ratio (E/M ratio) were all significantly higher compared with those in patients with non-eCRSwNP (p < 0.05). To diagnose eCRSwNP, the highest area under the curve (0.803) was determined for nNO. At a cutoff of >329 parts per billion (ppb), the sensitivity was 83.30% and the specificity was 71.70%. However, the levels of plasma cytokines Th1/Th2 were not significantly different between the histological types of CRSwNP (p > 0.05). Conclusion: Measurement of nNO is useful for the early diagnosis of eCRSwNP.

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Mycoplasma pneumoniaeandChlamydophila pneumoniae: a comparative study in patients with nasal polyposis and healthy controls

The Journal of Laryngology & Otology ◽

10.1017/s0022215115001590 ◽

2015 ◽

Vol 129 (9) ◽

pp. 865-869 ◽

Cited By ~ 1

Author(s):

D G Ioannidis ◽

V A Lachanas ◽

Z Florou ◽

J G Bizakis ◽

E Petinaki ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Real Time ◽

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Inferior Turbinate ◽

Sinus Surgery ◽

Control Group ◽

Chain Reaction ◽

Tissue Samples ◽

Polymerase Chain

AbstractIntroduction:The role played byMycoplasma pneumoniaeandChlamydophila pneumoniaein the pathogenesis of chronic rhinosinusitis with nasal polyps has been the object of ongoing debate. We used real-time polymerase chain reaction to investigate the prevalence of both microorganisms in the nasal tissue samples of patients and controls.Methods:We extracted DNA from nasal polyp samples obtained during functional endoscopic sinus surgery and the inferior turbinate samples of controls undergoing septoplasty. We used the highly sensitive real-time polymerase chain reaction to detect the presence ofM pneumoniaeandC pneumoniaeDNA.Results:Patients with chronic rhinosinusitis with nasal polyps consisted of 62 individuals (39 men; mean age 51 years); the control group consisted of 24 individuals (13 men; mean age 45 years). All samples from both groups were negative forM pneumoniaeandC pneumoniaeDNA.Conclusion:We have demonstrated that the likelihood ofM pneumoniaeandC pneumoniaeacting as an ongoing inflammatory stimulus in chronic rhinosinusitis with nasal polyps is slim.

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Inhibition of nitric oxide synthesis promotes increased mortality despite the reduction of parasitemia in Plasmodium berghei-infected mice

Research Society and Development ◽

10.33448/rsd-v10i1.11805 ◽

2021 ◽

Vol 10 (1) ◽

pp. e27810111805

Author(s):

Aline da Silva Barbosa ◽

Mayani Costa Ribeiro Temple ◽

Everton Luiz Pompeu Varela ◽

Antonio Rafael Quadros Gomes ◽

Edvaldo Lima Silveira ◽

...

Keyword(s):

Nitric Oxide ◽

Plasmodium Berghei ◽

Thiobarbituric Acid ◽

Trolox Equivalent Antioxidant Capacity ◽

Control Group ◽

Histopathological Study ◽

Progression Rate ◽

Tissue Samples ◽

Trolox Equivalent ◽

Inflammatory Processes

Nitric oxide (NO) is an important mediator molecule in inflammatory processes, but its role in the pathophysiology of malaria is still uncertain. To investigate the NO synthesis inhibition on the oxidative changes induced by Plasmodium berghei infection in mice, malaria was induced in 150 animals, of which 75 animals were treated with the NO inhibitor L-NAME; the remaining animals were sham controls. All animals underwent euthanasia 1, 5, 10, 15, or 20 days after infection for the collection of lungs, brain, and blood. Parasitemia was determined, and the survival of the animals was evaluated. Tissue samples were assayed for nitrites and nitrates (NN), thiobarbituric acid reactive substances (TBARS), and total Trolox equivalent antioxidant capacity (TEAC). A histopathological study was performed. Mortality rates in the L-NAME group were always higher than those in the controls. In the brain, NN was lower in the L-NAME group. Parasitemia and its progression rate were greater in the control group. By the 5th day of infection, mice treated with L-NAME showed cerebral edema and interstitial pneumonia of greater intensity than controls. In conclusion, the anti-inflammatory and hemodynamic effects of NO surpass its pro-oxidant role in murine malaria.

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Protective Effects of Bacillus amyloliquefaciens 40 Against Clostridium perfringens Infection in Mice

Frontiers in Nutrition ◽

10.3389/fnut.2021.733591 ◽

2021 ◽

Vol 8 ◽

Author(s):

Zipeng Jiang ◽

Wentao Li ◽

Weifa Su ◽

Chaoyue Wen ◽

Tao Gong ◽

...

Keyword(s):

Nitric Oxide ◽

Clostridium Perfringens ◽

Relative Abundance ◽

Bacillus Amyloliquefaciens ◽

Infected Group ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

No Production ◽

Mrna Levels ◽

Protective Effects

This study aimed to investigate the protective effects of Bacillus amyloliquefaciens (BA40) against Clostridium perfringens (C. perfringens) infection in mice. Bacillus subtilis PB6 was utilized as a positive control to compare the protective effects of BA40. In general, a total of 24 5-week-old male C57BL/6 mice were randomly divided into four groups, with six mice each. The BA40 and PB6 groups were orally dosed with resuspension bacteria (1 × 109 CFU/ml) once a day, from day 1 to 13, respectively. In the control and infected groups, the mice were orally pre-treated with phosphate-buffered saline (PBS) (200 μl/day). The mice in the infected groups, PB6 + infected group and BA40 + infected group, were orally challenged with C. perfringens type A (1 × 109 CFU/ml) on day 11, whereas the control group was orally dosed with PBS (200 μl/day). The results showed that the BA40 group ameliorated intestinal structure damage caused by the C. perfringens infection. Furthermore, the inflammatory responses detected in the infected groups which include the concentrations of IL-1β, TNF-α, IL-6, and immunoglobulin G (IgG) in the serum and secretory immunoglobulin (SigA) in the colon, and nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) activity in the jejunum, were also alleviated (P < 0.05) by BA40 treatment. Similarly, cytokines were also detected by quantitative PCR (qPCR) in the messenger RNA (mRNA) levels, and the results were consistent with the enzyme-linked immunosorbent assay (ELISA) kits. Additionally, in the infected group, the mRNA expression of Bax and p53 was increasing and the Bcl-2 expression was decreasing, which was reversed by BA40 and PB6 treatment (P < 0.05). Moreover, the intestinal microbiota imbalance induced by the C. perfringens infection was restored by the BA40 pre-treatment, especially by improving the relative abundance of Verrucomicrobiota (P < 0.05) and decreasing the relative abundance of Bacteroidetes (P < 0.05) in the phyla level, and the infected group increased the relative abundance of some pathogens, such as Bacteroides and Staphylococcus (P < 0.05) in the genus level. The gut microbiota alterations in the BA40 group also influenced the metabolic pathways, and the results were also compared. The purine metabolism, 2-oxocarboxylic acid metabolism, and starch and sucrose metabolism were significantly changed (P < 0.05). In conclusion, our results demonstrated that BA40 can effectively protect mice from C. perfringens infection.

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Evaluation of MMP-12 expression in chronic rhinosinusitis with nasal polyposis

Rhinology Journal ◽

10.4193/rhin21.320 ◽

2021 ◽

Vol 0 (0) ◽

pp. 0-0

Author(s):

S. Lygeros ◽

G. Danielides ◽

G.C. Kyriakopoulos ◽

K. Grafanaki ◽

F. Tsapardoni ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Gene Expression Regulation ◽

Statistical Significance ◽

Sinus Surgery ◽

Mrna Levels ◽

Tissue Samples ◽

Potential Implication ◽

Protein Levels ◽

Healthy Mucosa ◽

The Difference

Background: The purpose of this study was to evaluate the expression of MMP-12 in patients with chronic rhinosinusitis with polyps (CRSwNP). Methodology: Tissue samples from 37 patients with CRSwNP undergoing functional endoscopic sinus surgery and healthy mucosa specimens from 12 healthy controls were obtained intraoperatively. The mRNA and protein expression levels of MMP-12 were quantified by real-time polymerase chain reaction and Western blotting, respectively. Results: mRNA levels of MMP-12 were significantly elevated in the CRSwNP tissue samples compared to those in control ones. The protein levels of MMP-12 showed a trend of increasing but with no statistical significance. Conclusions: Elevation of MMP-12 in patients with CRSwNP suggests its potential implication in the pathogenesis of the disease. The difference in the expression profile observed between mRNA and protein levels could be due to post-translational gene expression regulation. Our findings provide evidence that MMP-12 along with other MMPs may serve as a biomarker and therapeutic target in the management of the disease.

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Measurement of Nasal Nitric Oxide in Chronic Rhinosinusitis and Its Relationship to Patient-Reported Outcome: A Longitudinal Pilot Study

Ear Nose & Throat Journal ◽

10.1177/0145561319880624 ◽

2019 ◽

pp. 014556131988062 ◽

Cited By ~ 1

Author(s):

Cecilia Alexandersson ◽

Lisa Tuomi ◽

Anna-Carin Olin

Keyword(s):

Nitric Oxide ◽

Chronic Rhinosinusitis ◽

Statistical Significance ◽

Measurement Techniques ◽

Control Group ◽

Healthy Controls ◽

Nasal Nitric Oxide ◽

Patient Reported ◽

Significant Change ◽

Snot 22

Objective: To assess whether nasal nitric oxide (nNO) levels differ between healthy and sick sinuses in chronic rhinosinusitis (CRS). A secondary aim was to assess whether nNO levels change after treatment of CRS and whether there is an association with radiological findings or symptoms. Method: Three groups of 12 participants each were examined: patients with CRS without polyposis (CRS group), patients with symptoms of CRS but radiologically normal sinuses (symptoms-only), and healthy controls. Measurements of nNO were carried out using aspiration method and humming maneuver. All participants completed the Sino-Nasal Outcome Test (SNOT-22). A second nNO measurement was done after treatment in the CRS group (n = 9) and the healthy control group (n = 12). Results: Nasal NO did not differ between any of the groups with any of the measurement techniques. There was a trend toward lower nNO values in the CRS group compared with the symptoms-only group and healthy controls, but it did not reach statistical significance. The SNOT-22 demonstrated inferior values for the CRS and symptoms-only groups compared with the healthy controls. At follow-up, no statistically significant change was found for the nNO measurements in either group. Conclusion: Irrespective of occluded or open ostiomeatal complexes, no statistically significant differences in nNO were found in CRS compared with healthy controls using aspiration and humming methods. Treatment of CRS improved sinus patency without accompanying a significant change in nNO. This study can therefore not conclude that nNO can be used as a diagnostic tool for CRS without polyposis.

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Effects of Intermittent Mild Cold Stimulation on mRNA Expression of Immunoglobulins, Cytokines, and Toll-Like Receptors in the Small Intestine of Broilers

Animals ◽

10.3390/ani10091492 ◽

2020 ◽

Vol 10 (9) ◽

pp. 1492

Author(s):

Shuang Li ◽

Jianhong Li ◽

Yanhong Liu ◽

Chun Li ◽

Runxiang Zhang ◽

...

Keyword(s):

Mrna Expression ◽

Positive Impact ◽

Control Group ◽

Mrna Levels ◽

Intestinal Immunity ◽

Toll Like Receptors ◽

Cold Stimulation ◽

Tissue Samples ◽

Group Iii ◽

Mrna Expression Levels

Appropriate cold stimulation can improve immune function and stress tolerance in broilers. In order to investigate the effect of intermittent mild cold stimulation on the intestinal immunity of broilers, 240 healthy one-day-old Ross 308 chickens were randomly divided into three groups: the control group (CC) housed in climatic chambers under usual rearing ambient temperature with a gradual 3.5 °C decrease per week; group II (C3) and group III (C6) to which cold stimulation at 3 °C below the temperature used in CC was applied every two days for 3 and 6 h, respectively, from day 15 to 35, and at the same temperature used in CC from day 35 to 43. The mRNA expression levels of immunoglobulins (IgA and IgG), cytokines (IL2, IL6, IL8, IL17, and IFNγ), and Toll-like receptors (TLR2, TLR4, TLR5, TLR7, and TLR21) were investigated in duodenum, jejunum, and ileum tissue samples on days 22, 29, 35, and 43. From day 15 to 35, mRNA expression of IL2 and IFNγ was increased in the intestine of broilers. After one week of cold stimulation on day 43, mRNA levels of immunoglobulins, cytokines, and Toll-like receptors (TLRs) stabilized. Collectively, the findings indicate that cold stimulation at 3 °C below the usual rearing temperature had a positive impact on intestinal immunity of broilers.

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Increased Tissue Expression of Lectin-Like Oxidized LDL Receptor-1 (LOX-1) Is Associated with Disease Severity in Chronic Rhinosinusitis with Nasal Polyps

Diagnostics ◽

10.3390/diagnostics10040246 ◽

2020 ◽

Vol 10 (4) ◽

pp. 246

Author(s):

Manabu Nishida ◽

Sachio Takeno ◽

Kohta Takemoto ◽

Daisuke Takahara ◽

Takao Hamamoto ◽

...

Keyword(s):

Oxidative Stress ◽

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Ldl Receptor ◽

Control Group ◽

Environment Interaction ◽

Low Density ◽

Mrna Levels ◽

Protein Distribution ◽

Significant Difference

Background: The oxidative stress, induced by both environmental and intrinsic stimuli, underlies the onset and persistency of chronic rhinosinusitis (CRS). Scavenger receptors (SRs) are a broad family of transmembrane receptors involved in a dysfunctional host–environment interaction through a reaction with reactive oxygen species (ROS) production. Objective: We hypothesized possible roles of two major SRs in CRS pathology that can translate to clinical phenotypes or histological subtypes: lectin-like oxidized low-density lipoproteins (LDL) receptor-1 (LOX-1) and scavenger receptor class B type 1 (SR-B1). Patients and Methods: We collected ethmoid sinus mucosa specimens and blood samples from patients with CRS with nasal polyps (CRSwNP; n = 31) or CRS without NP (CRSsNP; n = 13) and 19 control subjects. We performed an RT-PCR analysis, ELISA assay, and immunostaining to determine the expressions and distributions of LOX-1 and SR-B1. Results: The CRSwNP group showed a significant increase in LOX-1 mRNA expression compared to the control group. There was no significant difference in SR-B1 mRNA levels among the three groups. The LOX-1 mRNA levels were positively correlated with the sinus computed tomography (CT) scores. Sinus tissue, but not serum samples, showed elevated concentrations of LOX-1 protein in the CRSwNP group versus the control group. The LOX-1 protein distribution was localized in inflammatory cells and vascular endothelial cells. Conclusion: LOX-1 is a major receptor for oxidized low-density lipoprotein produced by oxidative stress. This is the first study to report alterations in LOX-1 expression and production triggered by persistent inflammatory processes in CRSwNP patients. Our findings reveal complex but important roles for SRs that may contribute to the onset of different CRS phenotypes.

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Correlation Between HMGB1 and TLR4 Expression in Sinonasal Mucosa in Patients With Chronic Rhinosinusitis

Ear Nose & Throat Journal ◽

10.1177/0145561319858915 ◽

2019 ◽

Vol 98 (10) ◽

pp. 599-605

Author(s):

Mohammad Hossein Taziki ◽

Ramin Azarhoush ◽

Mohammad Mahdi Taziki ◽

Mahdieh Naghavi-Alhosseini ◽

Naeme Javid ◽

...

Keyword(s):

Real Time ◽

Chronic Rhinosinusitis ◽

Messenger Rna ◽

Pearson Correlation ◽

Expression Patterns ◽

High Mobility ◽

Upper Airway ◽

Control Group ◽

Control Analysis ◽

Embedded Blocks

Objectives: Chronic rhinosinusitis (CRS) is one of the most common inflammations in the upper airway. Despite the wide prevalence of CRS, the pathogenesis of this disease is poorly understood. Several components of the innate immune system may play a significant role in CRS, including Toll-like receptor 4 (TLR4), TLR9, and high-mobility group box 1 protein (HMGB1). This study was conducted to determine the expression of TLR4, TLR9, HMGB1, and pNFκ-B p65 in paraffin-embedded blocks of patients with CRS with nasal polyps compared with those of the control group. Methods: Twenty-six formalin-fixed, paraffin-embedded samples from patients with confirmed CRS and 26 patients undergoing septoplasty due to anatomic variations and no other inflammatory nasal diseases as the control group were assessed. Expression patterns of HMGB1, TLR9, TLR4, and pNFκ-B p65 genes were examined using real-time quantitative reverse transcription polymerase chain reaction (Real-Time qRT-PCR). Statistical analyses were performed with SPSS and analyzed using unpaired 2-tailed t tests or 1-way analysis of variance. Results: Real-time PCR showed that the expression level of HMGB1 messenger RNA was significantly increased in the tissues of patients with CRS compared with controls ( P < .05). The other 3 genes were also upregulated in the patients, but were not significant compared with control. Analysis of the Pearson correlation coefficient ( r) revealed a significant positive correlation between HMGB1 and TLR4 ( r = 0.79, P < .05) in patients and negative correlation between TLR4 and NfκB in the control group ( r = 0.94; P < .05). Conclusions: Both HMGB1 and TLR4 are increased in the paranasal sinus mucosa of patients with CRS. These results suggest a possible contribution of HMGB1 and its internal receptor (TLR4) in the pathophysiology of CRS.

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