scholarly journals CD133, a Progenitor Cell Marker, is Reduced in Nasal Polyposis and Showed Significant Correlations with TGF-β1 and IL-8

Author(s):  
Wagner Vargas Souza Lino ◽  
André Luis Lacerda Bachi ◽  
José Arruda Mendes Neto ◽  
Gabriel Caetani ◽  
Jônatas Bussador do Amaral ◽  
...  

Abstract Introduction Combination of chronic inflammation and an altered tissue remodeling process are involved in the development of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Studies demonstrated that mesenchymal stem cells expressing the progenitor gene CD133 were involved in a significant reduction of the chronic inflammatory process in the polypoid tissue. Objective To evaluate the levels of CD133 (Prominin-1) in nasal polypoid tissue and its correlation with interleukin-8 (IL-8) and transforming growth factor β1 (TGF-β1). Methods A total of 74 subjects were divided in the following groups: control group (n = 35); chronic rhinosinusitis with nasal polyps nonpresenting comorbid asthma and aspirin intolerance (CRSwNPnonAI) group (n = 27); and chronic rhinosinusitis with nasal polyps presenting comorbid asthma and aspirin intolerance (CRSwNPAI) group (n = 12). Histologic analysis and also evaluation of the concentration of CD133, IL-8, and TGF-β1 by enzyme-linked immunosorbent assay (ELISA) kits were performed in nasal tissue obtained from nasal polypectomy or from middle turbinate tissue. Results Higher eosinophilic infiltration was found in both CRSwNP groups by histologic analysis. Lower levels of TGF-β1 and IL-8 were observed in both CRSwNP groups when compared with the control group, whereas the CD133 levels were significantly reduced only in the CRSwNPnonAI group compared with the control group. Conclusion It was demonstrated that the nasal mucosa presenting polyposis showed a significant reduction of CD133 levels, and also that this reduction was significantly correlated with the reduction of TGF-β1 levels, but not with IL-8 levels. Therefore, these findings may be involved in the altered inflammatory and remodeling processes observed in the nasal polyposis.

2020 ◽  
Vol 34 ◽  
pp. 205873842092391 ◽  
Author(s):  
Min-na Dong ◽  
Yun Xiao ◽  
Yun-fei Li ◽  
Dong-mei Wang ◽  
Ya-ping Qu ◽  
...  

Intravenous Xuebijing (XBJ) therapy suppresses paraquat (PQ)-induced pulmonary fibrosis. However, the mechanism underlying this suppression remains unknown. This work aimed to analyze the miR-140-5p-induced effects of XBJ injection on PQ-induced pulmonary fibrosis in mice. The mice were arbitrarily assigned to four groups. The model group was administered with PQ only. The PQ treatment group was administered with PQ and XBJ. The control group was administered with saline only. The control treatment group was administered with XBJ only. The miR-140-5p and miR-140-5p knockout animal models were overexpressed. The gene expression levels of miR-140-5p, transglutaminase-2 (TG2), β-catenin, Wnt-1, connective tissue growth factor (CTGF), mothers against decapentaplegic homolog (Smad), and transforming growth factor-β1 (TGF-β1) in the lungs were assayed with quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis. The levels of TGF-β1, CTGF, and matrix metalloproteinase-9 (MMP-9) in the bronchoalveolar lavage fluid were assessed by enzyme-linked immunosorbent assay (ELISA). Hydroxyproline (Hyp) levels and pulmonary fibrosis were also scored. After 14 days of PQ induction of pulmonary fibrosis, AdCMV-miR-140-5p, and XBJ upregulated miR-140-5p expression; blocked the expressions of TG2, Wnt-1, and β-catenin; and decreased p-Smad2, p-Smad3, CTGF, MMP-9, and TGF-β1 expressions. In addition, Hyp and pulmonary fibrosis scores in XBJ-treated mice decreased. Histological results confirmed that PQ-induced pulmonary fibrosis in XBJ-treated lungs was attenuated. TG2 expression and the Wnt-1/β-catenin signaling pathway were suppressed by the elevated levels of miR-140-5p expression. This inhibition was pivotal in the protective effect of XBJ against PQ-induced pulmonary fibrosis. Thus, XBJ efficiently alleviated PQ-induced pulmonary fibrosis in mice.


OTO Open ◽  
2019 ◽  
Vol 3 (3) ◽  
pp. 2473974X1987507
Author(s):  
Ashley Lonergan ◽  
Theoharis Theoharides ◽  
Eirini Tsilioni ◽  
Elie Rebeiz

This pilot study was undertaken to isolate and quantify substance P (SP) and hemokinin 1 (HK-1) in the nasal lavage fluid of patients with chronic rhinosinusitis with nasal polyps to better elucidate the pathophysiology underlying this inflammatory process, which remains poorly understood. Mucus samples were collected from this introductory cohort of 10 patients diagnosed with chronic rhinosinusitis with nasal polyps at Tufts Medical Center (Boston, Massachusetts). Relative levels of SP and HK-1 were measured with enzyme-linked immunosorbent assay methods. Both inflammatory neuropeptides were found in detectable and comparable amounts in patient samples and in concentrations up to 100-fold those established in past literature. The presence of SP and HK-1 necessitates further investigation into their role in nasal polyposis and the potentiation of the chronic inflammation inherent to chronic rhinosinusitis. Downregulating these peptides could therefore provide novel treatment targets to manage this disease process.


Author(s):  
Soo Kyoung Park ◽  
Rui-Ning Han ◽  
Jun Xu ◽  
Sun Hee Yeon ◽  
Sung Bok Lee ◽  
...  

Background and Objectives The nucleotide-binding oligomerization domain-like receptor (NLRP) 3 is known as a member of the NLR family, and it has been confirmed that the NLRP3 inflammasome is associated with various diseases such as asthma, inflammatory bowel disease, metabolic disorders and multiple sclerosis, as well as other auto-immune and auto-inflammatory diseases. However, the role of NLRP3 in chronic rhinosinusitis with nasal polyps (CRSwNP) has not yet been explored.Subjects and Method Forty-four specimens of nasal polyps and 25 specimens of uncinate processes were collected from patients with chronic rhinosinusitis with nasal polyps, and 25 specimens of uncinate tissues were collected from patients who underwent other rhino-surgeries. The western blot assay was employed to analyze the expression of NLRP3; interleukin (IL)-1β and IL-17A were detected using immunohistochemistry and real-time polymerase chain reaction. The production of lipopolysaccharide (LPS) induced IL-1β and IL-17A with or without the NLRP3 inflammasome inhibitor (MCC950) was measured using an enzyme linked immunosorbent assay in cultured dispersed nasal polyp cells.Results NLRP3 showed a high level of expression in nasal polyps than in the control group (<i>p</i><0.01). The expression of IL-1β and IL-17A was significantly higher in nasal polyps in the CRSwNP group than in the control group (<i>p</i><0.05). LPS-induced production of IL-1β was significantly suppressed by treatment with the NLRP3 inflammasome inhibitor (<i>p</i><0.05).Conclusion The NLRP3 inflammasome plays an essential role in the pathogenesis of CRSwNP, and thus MCC950 can be considered a prospective therapeutic for NLRP3 inflammasome-mediated inflammation in nasal polyps. Our data provide new evidence that IL-17A is involved in inflammasome-associated inflammation in nasal polyps.


2013 ◽  
Vol 4 (2) ◽  
pp. ar.2013.4.0055 ◽  
Author(s):  
Ba Luo ◽  
Liu Feng ◽  
Du Jintao ◽  
Liu Yafeng ◽  
Liu Shixi ◽  
...  

Chronic rhinosinusitis (CRS) presents distinct inflammatory and remodeling patterns in different populations and environments. Tibetan ethnic groups live at high altitudes and in cold weather conditions. We sought to examine whether Tibetans exhibit distinct CRS pathology or characteristics. Sinonasal polyps and mucosal tissue were obtained from 14 Tibetan patients with CRS and nasal polyps (CRSwNPs), 13 patients with CRS without nasal polyps (CRSsNPs), and 12 Tibetan controls. Tissue homogenates and serum samples were assayed for several T-helper (TH) cell cytokines and mediators using enzyme linked immunosorbent assay profiles were measured using quantity polymerase chain reaction. Several key inflammatory cells were examined for immunohistochemical markers. CRSwNPs were characterized by increased mediator promoting eosinophilic inflammation (interleukin [IL]-5, eosinophil cationic protein, and total immunoglobulin E) and slight synergism with expression of IL-8, IL-2sRa, IL-1beta, IL-6, and myeloperoxidase, and a predominance of eosinophils, mast cells, and neutrophils. GATA-3 transcription factor was significantly increased and Foxp3 showed a tendency to be impaired in CRSwNPs compared with controls. CRSsNPs were characterized by significantly high levels of transforming growth factor beta1, increased interferon γ, and a significant enhancement of Foxp3 and T-beta compared with CRSwNPs. There were reduced numbers of inflammatory cells but increased levels of macrophages in CRSsNPs. Compared with CRSsNPs, CRSwNPs present a severe inflammatory reaction and show a TH2 milieu with apparently impaired regulatory T cells (Treg) function and increased inflammatory cells infiltration predominated by eosinophilic and mast cells. In contrast, TH1 polarization with enhanced Treg function and increased levels of macrophages appear in CRSsNPs.


2019 ◽  
Vol 33 (5) ◽  
pp. 490-499 ◽  
Author(s):  
Yimin Li ◽  
Guojing Tan ◽  
Jie Liu ◽  
Xia Ke ◽  
Yang Shen ◽  
...  

Background Relaxin is a small peptide hormone that regulates extracellular matrix remodeling and reduces fibrosis in a number of organs. Little is known about its impact on chronic rhinosinusitis with nasal polyps (CRSwNP); thus, we aimed to determine the expression of human H2 relaxin (relaxin-2) and its role in tissue remodeling in CRSwNP. Methods Patients were enrolled and divided into the following groups: CRS with NP (CRSwNP; n = 20), CRS without NP (CRSsNP; n = 20), and controls (n = 15). Tissue samples were analyzed by Masson trichrome staining for collagen, while the location and expression of relaxin-2, transforming growth factor beta 1 (TGF-β1), and phosphorylated (p) Smad2/Smad3 were analyzed by immunohistochemistry and Western blot. The expression of relaxin-2, Smad2, Smad3, and TGF-β1 mRNA was tested by quantitative polymerase chain reaction (qPCR). Ex vivo NP were treated with relaxin-2 (n = 15) or TGF-β1 (n = 15). Collagen type I (collagen I), relaxin-2, and TGF-β1 levels in the culture supernatants were examined by enzyme-linked immunosorbent assay, while pSmad2/Smad3 in culture pellets was analyzed by Western blot, and the expression of Smad2 and Smad3 mRNA was tested by qPCR. Results The collagen, relaxin-2, TGF-β1, and pSmad2/Smad3 protein expression levels were significantly decreased in the CRSwNP group compared with the CRSsNP group ( P < .05). The expression of relaxin-2, Smad2, Smad3, and TGF-β1 mRNA in the CRSsNP group was significantly higher than in the CRSwNP and control groups ( P < .05). Compared with the ex vivo controls, in CRSwNP, the levels of TGF-β1, collagen I, pSmad2/Smad3, Smad2, and Smad3 were markedly decreased after relaxin-2 treatment. However, relaxin-2, collagen I, pSmad2/Smad3, Smad2, and Smad3 were remarkably increased after TGF-β1 treatment. Conclusions The antifibrotic effects of relaxin-2 may play a role in tissue remodeling in CRSwNP, but the detailed mechanism deserves further study.


2018 ◽  
Vol 132 (8) ◽  
pp. 724-728
Author(s):  
O Ismi ◽  
T Kara ◽  
G Polat ◽  
O Bobusoglu ◽  
Y Vayısoglu ◽  
...  

AbstractBackgroundAlthough the role of neurotrophins such as nerve growth factor and brain-derived neurotrophic factor in nasal polyps development has been studied, the contribution of neurotrophin-3 has not been evaluated yet. This study aimed to investigate the possible role of neurotrophin-3 in nasal polyps pathogenesis.MethodsThe study group comprised 70 non-allergic nasal polyps patients and the control group consisted of 53 patients with middle turbinate concha bullosa. Specimens were taken, during surgery, from the ethmoid sinus nasal polyps in the nasal polyps group and from the lateral part of the middle turbinate concha bullosa in the control group. Tissue and serum levels of neurotrophin-3 were assessed by immunohistochemistry and enzyme-linked immunosorbent assay, respectively.ResultsNasal polyps patients had higher tissue neurotrophin-3 scores (p< 0.001). There was no statistically significant difference between groups regarding serum neurotrophin-3 levels (p= 0.417). Tissue neurotrophin-3 staining scores in the nasal polyps group had no statistically significant correlation with Lund–Mackay scores (p= 0.792).ConclusionNeurotrophin-3 may have a local effect in nasal polyps pathogenesis, without joining systemic circulation.


Author(s):  
Rogério Pezato ◽  
Luciano Lobato Gregório ◽  
Claudina Pérez-Novo ◽  
Thiago Ferreira Pinto Bezerra ◽  
Eduardo Macoto Kosugi

Abstract Introduction Nasal polyposis is a disease characterized by a mechanical dysfunction of the nasal mucosa, closely related to the unique makeup of its extracellular matrix, which develops as the result of an anomalous tissue remodeling process.Transforming growth factor beta 1 (TGF-β1) is reduced not only in the nasal polypoid tissue, but also in the plasma of aspirin-intolerant patients. These patients exhibit an imbalance in the production of eicosanoids characterized by an increase in leukotrienes. Thus, it is important that the relationship between the production of leukotrienes and TGF-β1 be assessed. Objective To evaluate the effects of the cysteinyl leukotriene (CysLT) receptor antagonist montelukast on the systemic production of TGF-β1 in patients with nasal polyposis, with or without concomitant aspirin intolerance. Methods The sample comprised 48 individuals with diagnosis of nasal polyposis and 15 healthy controls for comparison of the baseline TGF-β1 levels in the peripheral blood and after treatment with CysLT receptor antagonist montelukast in the nasal-polyposis group. Results There was no difference in the change in TGF-β1 levels after the treatment with montelukast in the subgroup of patients with polyposis and asthma (p = 0.82) and in the subgroup with polyposis, asthma, and aspirin intolerance (p = 0.51). Conclusion we found no impact of the therapy with a leukotriene receptor blocker on the production of TGF-β1, making the antileukotriene therapy a highly questionable choice for the treatment of nasal polyposis, particularly from the standpoint of seeking to modify the remodeling process in this disease.


2016 ◽  
Vol 36 (8) ◽  
pp. 802-812 ◽  
Author(s):  
XH Chang ◽  
A Zhu ◽  
FF Liu ◽  
LY Zou ◽  
L Su ◽  
...  

Nano nickel oxide (NiO), widely used in industry, has recently been discovered to have pulmonary toxicity. However, no subchronic exposure studies about nano NiO-induced pulmonary fibrosis have been reported. The objective of this study was to investigate pulmonary fibrosis induced by nano NiO and its potential mechanism in rats. Male Wistar rats ( n = 40, 200–240 g) were randomized into control group, nano NiO groups (0.015, 0.06, and 0.24 mg/kg), and micro NiO group (0.024 mg/kg). All rats were killed to collect lung tissue after intratracheal instillation of NiO particles twice a week for 6 weeks. To identify pulmonary fibrosis, Masson trichrome staining, hydroxyproline content, and collagen protein expression were performed. The results showed widespread lung fibrotic injury in histological examination and increased content of hydroxyproline, collagen types I and III in rat lung tissue exposed to nano NiO. To explore the potential pulmonary fibrosis mechanism, transforming growth factor beta 1 (TGF- β1) content was measured by enzyme-linked immunosorbent assay, and the messenger RNA expression of key indicators was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The TGF- β1 content was increased in nano NiO exposure groups, as well as the upregulated gene expression of TGF- β1, Smad2, Smad4, matrix metalloproteinase, and tissue inhibitor of metalloproteinase. The findings indicated that nano NiO could induce pulmonary fibrosis, which may be related to TGF- β1 activation.


2017 ◽  
Vol 3 (1) ◽  
pp. 15 ◽  
Author(s):  
Hasret Ecevit ◽  
Kubra Gunduz ◽  
Nilufer Bilgic ◽  
Muzeyyen Izmirli ◽  
Bulent Gogebakan

<p>Thymoquinone, one of the essential oil in the structure of cumin, is used for alternative therapy for many diseases from past to present. It was shown to have anti-carcinogenic and anti-inflammatory effects, as well as positive effects on fibrosis. However, there is no study on the effect of thymoquinone on cancer and fibrosis mechanism in bronchial epithelium cell line BEAS-2B. In our study, the effect of thymoquinone on cell viability and transforming growth factor-beta 1 (TGF-β1) level, which has an important role in the regulation of many biological processes including cancer and fibrosis-associated signal transduction, was evaluated. BEAS-2B cells were exposed to thymoquinone at 0–80 μmol/L concentrations for 24-, 48- and 72-hour durations. Cell viability was evaluated with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. TGF-β1 level was determined with enzyme-linked immunosorbent assay (ELISA) method from the collected supernatant. Cell viability was found to be increased at all concentrations and durations (10–80 μmol/L; 24, 48 and 72 h) according to the control group (0 μmol/L; thymoquinone in ethanol) (p &lt; 0.0001). Moreover, thymoquinone was found to increase the level of TGF-β1 only at 80 μmol/L concentration and 24-hour exposure period (0 μmol/L, 53.41 ± 18.44 pgr/ml TGF-β1; 80 μmol/L, 174.5 ± 80.03 pgr/ml TGF-β1). As a result, thymoquinone was found to increase cell proliferation and encourage TGF-β1 release.</p>


Author(s):  
Sritharadol Rutthapol ◽  
Chunhachaichana Charisopon ◽  
Kumlungmak Sukanjana ◽  
Buatong Wilaiporn ◽  
Dechraksa Janwit ◽  
...  

ABSTRACT This study evaluated the effect of mupirocin topical spray on burn wound healing in a rat model. Fifteen male Sprague Dawley rats were used to create full-thickness burns on the rat dorsum using a cylindrical stainless steel rod. The rats were topically treated with normal saline solution (NSS), mupirocin spray, ointment, and solution. The wound size and morphological evaluation were investigated by photographs and clinical criterions for wound healing. The histology was observed by hematoxylin and eosin (HandE) staining assay. The immunohistochemical study was evaluated by detection of transforming growth factor-beta 1 (TGF-β1), and the ratio of matrix metalloproteinase-9 to the tissue inhibitor of matrix metalloproteinase-1 (MMP-9/TIMP-1) was quantified using the enzyme-linked immunosorbent assay (ELISA) assay. A complete healing was observed at 28 days in all treatments. Mupirocin formulations accelerated the wound healing faster than NSS in size. However, the clinical criteria indicated a desirable skin appearance in the mupirocin spray and ointment treated groups. The histological evaluations showed no differences between the treatments while the immunohistochemical study revealed that all treatments reduced the level of TGF-β1 over time, particularly on day 28 in the mupirocin spray and ointment treated groups. The MMP-9/TIMP-1 ratio was significantly lower in the mupirocin spray and ointment treated groups than in the NSS and mupirocin solution groups. This study shows the safety and efficacy in the use of mupirocin topical spray. The topical mupirocin spray is an alternative suitable for development as a human topical anti-infective and wound protection spray.


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