Up-Regulation of Protease-Activated Receptor 2 in Allergic Rhinitis

2007 ◽  
Vol 116 (7) ◽  
pp. 554-558 ◽  
Author(s):  
Heung-Man Lee ◽  
Hyo Yeol Kim ◽  
Hee Joon Kang ◽  
Jeong Soo Woo ◽  
Sung Won Chae ◽  
...  

Objectives: We compared the patterns of PAR-2 messenger RNA (mRNA) and protein expression in the nasal mucosa of subjects with and without allergic rhinitis. Methods: Biopsy specimens were obtained from 10 patients with allergic rhinitis and 10 normal controls. RNA was extracted from the nasal mucosa, and semiquantitative reverse transcription-polymerase chain reaction was performed for PAR-2. Tissue sections were immunostained for PAR-2 by use of specific antibody. Results: The expression levels of PAR-2 mRNA in allergic rhinitis nasal mucosa were significantly up-regulated as compared with those in normal nasal mucosa. PAR-2 immunoreactivity was observed in the epithelium and submucosal glands in both normal controls and subjects with allergic rhinitis. Stronger immunoreactivity for PAR-2 was observed in allergic rhinitis nasal mucosa as compared with normal nasal mucosa. Conclusions: These results suggest that PAR-2 may be involved in allergic nasal inflammation.

2007 ◽  
Vol 21 (4) ◽  
pp. 395-401 ◽  
Author(s):  
Eng Hooi Ooi ◽  
Peter-John Wormald ◽  
A. Simon Carney ◽  
Craig Lloyd James ◽  
Lor Wai Tan

Background Eosinophilic mucus chronic rhinosinusitis (EMCRS) patients are a subgroup of CRS with a poorer prognosis due to frequent recurrences of disease. The cathelicidin antimicrobial peptide (CAMP) is an important innate defense peptide but its role in CRS is not well characterized. The purpose of this study was to investigate CAMP mRNA and protein expression from EMCRS, CRS, and normal control patients. Methods Biopsy specimens of nasal mucosa and nasal polyps were taken from 59 CRS patients and 9 controls. CAMP mRNA and protein levels were analyzed by real-time quantitative reverse-transcriptase polymerase chain reaction, immunoassay, Western blot, and immunohistochemistry. Results The expression of CAMP mRNA was significantly increased in EMCRS patients compared with CRS patients (p = 0.0004). By immunohistochemistry, expression of CAMP was localized to nasal epithelial, submucosal glands, and inflammatory subepithelial cells. Western blotting confirmed the presence of CAMP in EMCRS, CRS, and control patients. However, we did not detect statistically significant differences in the protein levels in tissue homogenates between EMCRS, CRS, and control patients. Conclusion This study shows expression of CAMP in nasal mucosa supporting its role in innate defenses against inhaled pathogens. Although CAMP mRNA was up-regulated in EMCRS patients, there were no statistically significant differences in protein levels in the nasal mucosa of EMCRS compared with CRS patients and controls.


2009 ◽  
Vol 23 (4) ◽  
pp. 370-376 ◽  
Author(s):  
Joon Hwan Moon ◽  
Tae Hoon Kim ◽  
Heung Man Lee ◽  
Seung Hoon Lee ◽  
Whan Choe ◽  
...  

Background The purpose of this study was to investigate the expression and distribution of superoxide anion, NADPH oxidase (NOX)1, and NOX4 in healthy, allergic nasal mucosa and nasal polyps to evaluate the possible influence of oxidative stress on the development of allergic rhinitis and nasal polyps. Methods The expression and distribution of superoxide anion, NOX1 and NOX4 were evaluated in healthy and allergic nasal mucosa and nasal polyps, using dihydroethidium fluorescence, semiquantitative reverse transcriptase-polymerase chain reaction, immunohistochemistry, and Western blot. Results NOX1 and NOX4 were localized mainly in the epithelial layer, submucosal glands, vascular endothelium, and inflammatory cells in healthy and allergic nasal mucosa and nasal polyps. The cellular source that generated superoxide anion is also localized in the epithelial cells, submucosal glands, vascular endothelium, and inflammatory cells, demonstrating the similar sites of expression of NOX1 and NOX4 in healthy and allergic nasal mucosa and nasal polyps. NOX1 and NOX4 mRNA and proteins and superoxide anions had increased levels of expression in allergic nasal mucosa and nasal polyps compared with healthy nasal mucosa. Conclusions These results indicate that NOX1 and NOX4 may play an important role in reactive oxygen species production, contributing to the oxidative stress in allergic rhinitis and nasal polyp tissues.


1997 ◽  
Vol 273 (3) ◽  
pp. F380-F385 ◽  
Author(s):  
A. J. Lewington ◽  
B. J. Padanilam ◽  
M. R. Hammerman

Genes differentially expressed after acute renal ischemic injury were identified using differential display-polymerase chain reaction (DD-PCR). Messenger RNA for calcyclin, a member of the S100 family of calcium-binding proteins, is increased in kidneys by 6 h following ischemic injury to rats compared with sham surgery. The level of calcyclin mRNA is increased 10-fold by 1 day postinjury and declines thereafter. In situ hybridization demonstrates little calcyclin mRNA in kidneys of sham-operated rats. However, calcyclin protein is present in glomeruli and distal tubules (DT). Compared with kidneys from sham-operated controls, both calcyclin mRNA and protein expression are increased at 1-3 days following ischemic injury in the thick ascending limb of Henle, the DT, and in damaged regenerating segments of proximal tubules. By 7 days postischemia there is a reduction in mRNA and protein expression. Calcyclin could play a role in the regulation of renal cell proliferation and regeneration in the recovery process after acute ischemic injury.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Maria Lauriello ◽  
Alessandra Micera ◽  
Paola Muzi ◽  
Lino Di Rienzo Businco ◽  
Sergio Bonini

Background. Toll-like receptors (TLRs) represent a family of evolutionarily conserved proteins, that represent a fundamental link between innate and adaptive immune responses.Aim. The purpose of this study was to investigate the expression of TLR4 and TLR9 in the normal nasal mucosa and in the mucosa of subjects with different phenotypes of rhinitis.Methodology. A confocal analysis of TLR4 and TLR9 (co)expression was carried out on biopsies from the inferior turbinate obtained from 4 patients affected by persistent allergic rhinitis, 8 patients with chronic rhino-sinusitis, and 6 patients with vasomotor rhinitis The results were compared with those of specimens obtained from 4 subjects undergoing nasal surgery, but with signs of nasal inflammation.Results. TLR4 and TLR9 were expressed in the healthy nasal mucosa; TLR4 and TLR9 expression was significantly decreased in allergic rhinitis. TLR4 was over expressed in the epithelium of chronic rhino-sinusitis. Both TLRs were co-expressed in the sub-epithelial infiltrate of chronic and vasomotor rhinitis, even though this expression was higher in the former compared with the latter.Conclusions. This study indicates that TLR4 and TLR9 show a different pattern of expression in different phenotypes of rhinitis, possibly related to the type and severity of the disease.


2020 ◽  
Vol 35 (1) ◽  
pp. 26-35
Author(s):  
Jun Wang, MS ◽  
Xue Kang, MS ◽  
Zhi-Qun Huang, MS ◽  
Li Shen, MS ◽  
Qing Luo, MD ◽  
...  

Background Protease-activated receptor-2 (PAR-2)-modulated tight junctions (TJs) have been suggested to be involved in the pathogenesis of chronic inflammatory diseases. However, immunopathogenesis remains to be investigated among patients with allergic rhinitis (AR). Objective This study sought to investigate the role of PAR-2 in the modulation of epithelial barrier function and the expression of TJs in the nasal mucosa of AR patients. Methods The expression of TJs and PAR-2 of the nasal mucosa in AR patients and control subjects by immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting. In vitro, Primary human nasal epithelial cells (pHNECs) of AR patients were stimulated by Der p1 to analyze the correlation between PAR-2 and TJs expression. Der p1-induced pHNECs were treated with the PAR-2 agonist SLIGRL-NH2 and antagonist FSLLRY-NH2. Fluorescein isothiocyanate–dextran 4 kDa detection was employed as an indicator of epithelial permeability. Results Lower expression levels of TJs in the nasal epithelium of AR patients were observed in comparison with that in control subjects. The PAR-2 level was markedly increased following treatment with 1,000 ng/mL of Der p1 for 24 hours in a cellular model of AR. The expression of PAR-2 was increased in Der p1-induced pHNECs of AR patients and correlated inversely with zonula occlidens (ZO)-1 and claudin-1. Treatment with Der p1 further downregulated TJs expression and promoted an increased epithelial permeability in Der p1-induced pHNECs. Conclusions PAR-2 could downregulate the expression of ZO-1 and claudin-1, which is involved in epithelial barrier dysfunction in AR.


2006 ◽  
Vol 121 (7) ◽  
pp. 644-649 ◽  
Author(s):  
R Xu ◽  
G Xu ◽  
J Shi ◽  
W Wen

A growing body of literature suggests that cytokines play an important part in the pathogenesis of chronic nasal sinusitis. However, the mechanism by which the expression of cytokines in chronic nasal sinusitis is upregulated has not been well documented. The present study investigated the role of nuclear factor-kappa B (NF-κB) activation in upregulating the expression of interleukin-5, -6 and -8 (IL-5, IL-6 and IL-8). We titrated the levels of IL-5, IL-6 and IL-8 in nasal mucosa in 52 cases of chronic nasal sinusitis and 12 normal subjects using enzyme-linked immunosorbent assay. According to whether allergic rhinitis was associated or not, we subdivided the patients into the AR group (with allergic rhinitis) and the NAR group (without allergic rhinitis). Semi-quantitative reverse transcription-polymerase chain reaction and immunohistochemical staining were used to evaluate expression and activation of NF-κB P50 and P65 subunits in nasal mucosa. The correlation between activities of P50 and P65 and cytokines expression was analysed. Our results showed that IL-5, IL-6 and IL-8 in both the AR and NAR groups were strikingly elevated in comparison with the control group (all p < 0.01 for AR group; p < 0.05, 0.05, 0.01, respectively, for NAR group); and they were even higher in the AR group than those in the NAR group (p < 0.01, 0.05, 0.01, respectively). P50 and P65 mRNA levels in both AR and NAR groups were markedly greater than those in the control group (all p < 0.01); and the AR group had further higher levels as compared with the NAR group (both p < 0.05). Immunohistochemical study revealed that nucleus-positive rates of P50 and P65 in both AR and NAR groups were significantly higher than those of the control group (all p < 0.01), and they were much greater in the AR group in comparison with the NAR group (all p < 0.01). Pearson correlation analysis demonstrated that P50 and P65 nucleus-positive rates were closely correlated with IL-6 and IL-8 levels, but not IL-5, with a correlation coefficient of 0.49 for P50 and IL-6, 0.54 for P50 and IL-8, 0.61 for P65 and IL-6, and 0.66 for P65 and IL-8 (all p < 0.01). In conclusion, upregulated expression and activation of NF-κB P50 and P65 might be one of the mechanisms for induction of IL-6 and IL-8 expression in chronic nasal sinusitis. Association of allergic rhinitis with chronic nasal sinusitis further enhanced NF-κB activity, and subsequently lead to even stronger expression of IL-6 and IL-8. IL-5 expression appeared to be independent of NF-κB pathway in chronic nasal sinusitis.


Author(s):  
G. W. Hacker ◽  
I. Zehbe ◽  
J. Hainfeld ◽  
A.-H. Graf ◽  
C. Hauser-Kronberger ◽  
...  

In situ hybridization (ISH) with biotin-labeled probes is increasingly used in histology, histopathology and molecular biology, to detect genetic nucleic acid sequences of interest, such as viruses, genetic alterations and peptide-/protein-encoding messenger RNA (mRNA). In situ polymerase chain reaction (PCR) (PCR in situ hybridization = PISH) and the new in situ self-sustained sequence replication-based amplification (3SR) method even allow the detection of single copies of DNA or RNA in cytological and histological material. However, there is a number of considerable problems with the in situ PCR methods available today: False positives due to mis-priming of DNA breakdown products contained in several types of cells causing non-specific incorporation of label in direct methods, and re-diffusion artefacts of amplicons into previously negative cells have been observed. To avoid these problems, super-sensitive ISH procedures can be used, and it is well known that the sensitivity and outcome of these methods partially depend on the detection system used.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lauriana Alves Santana ◽  
Suellen Karoline Moreira Bezerra ◽  
Beatriz Mangueira Saraiva-Romanholo ◽  
Wellington Pereira Yamaguti ◽  
Iolanda de Fátima Lopes Calvo Tibério ◽  
...  

AbstractSome clinical situations require the use of oxygen therapy for a few hours without hypoxemia. However, there are no literature reports on the effects of acute oxygen therapy on the nasal mucosa. This study aimed to evaluate the acute effects of cold bubble humidification or dry oxygen on nasal Inflammation, oxidative stress, mucociliary clearance, and nasal symptoms. This is a randomized controlled cross-sectional study in which healthy subjects were randomly allocated into four groups: (1) CA + DRY (n = 8): individuals receiving dry compressed air; (2) OX + DRY (n = 8): individuals receiving dry oxygen therapy; (3) CA + HUMID (n = 7): individuals receiving cold bubbled humidified compressed air; (4) OX + HUMID (n = 8): individuals receiving cold bubbled humidified oxygen therapy. All groups received 3 L per minute (LPM) of the oxygen or compressed air for 1 h and were evaluated: total and differential cells in the nasal lavage fluid (NLF), exhaled nitric oxide (eNO), 8-iso-PGF2α levels, saccharin transit test, nasal symptoms, and humidity of nasal cannula and mucosa. Cold bubble humidification is not able to reduced nasal inflammation, eNO, oxidative stress, mucociliary clearance, and nasal mucosa moisture. However, subjects report improvement of nasal dryness symptoms (P < 0.05). In the conclusion, cold bubble humidification of low flow oxygen therapy via a nasal cannula did not produce any effect on the nasal mucosa and did not attenuate the oxidative stress caused by oxygen. However, it was able to improve nasal symptoms arising from the use of oxygen therapy.


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