Dong Z

The characterization of IL-17A expression in patients with chronic rhinosinusitis with nasal polyps.

Background Interleukin (IL)-17A, mainly produced by Th17 cells, was previously described as an inflammatory cytokine that induces a profile of proinflammatory cytokines, chemokines, and metalloproteinases. Recent studies have revealed that IL-17 is correlated with inflammatory lung disorders by triggering an accumulation of neutrophils. More recently, we have shown that the expression of IL-17 may be involved in the development of nasal polyps (NPs). Here, we describe the characterization of IL-17 expression in patients with chronic rhinosinusitis with nasal polyps (CRSwNPs) from northeast China. Methods Histopathological observations and immunohistochemical (IHC) staining for IL-17, IL-17RD, myeloperoxidase, and CD68 were performed on 52 specimens (42 NPs and 10 specimens of middle turbinate as normal control). Double IHC staining was performed to determine which cells expressed IL-17. The serum expression levels of IL-17 were determined by ELISA and the mRNA expression of IL-17 and Th17 cells transcription factor retinoid acid–related orphan receptor C (RORc) was determined by real-time quantitative polymerase chain reaction. Results 42.9% of CRSwNP specimens presented eosinophilic inflammation; 35.7% of CRSwNP specimens presented neutrophilic inflammation. Relatively higher mRNA expression levels of IL-17 and RORc were seen in CRSwNPs compared with the controls. A marked increase of IL-17 and IL-17RD proteins (p < 0.01) were seen in CRSwNP group. The expression levels of IL-17 and RORc did not differ between eosinophilic and noneosinophilic CRSwNPs (p > 0.05). However, high expression levels of IL-17RD were seen in noneosinophilic CRSwNPs compared with eosinophilic CRSwNPs (p < 0.05). The serum expression of IL-17 in CRSwNP patients was similar to healthy controls. The IL-17 expressing cells mainly were the macrophages as shown by double IHC staining. Conclusion Chinese CRSwNP patients showed an enhanced Th17 response regardless of eosinophilic or noneosinophilic inflammation. IL-17 may be involved in the development of NPs through its local immune modulation.

Proinflammatory impact of Staphylococcus aureus enterotoxin B on human nasal epithelial cells and inhibition by dexamethasone.

Background The pathophysiology and etiology of chronic rhinosinusitis with nasal polyps (CRSwNP) are poorly understood. Although a potential role of staphylococcal enterotoxins (SE) in the pathogenesis of CRSwNP has been detected, additional studies are needed on the impact of SE on nasal epithelial cells. The purpose of this study was to evaluate the impact of Staphylococcus aureus enterotoxin B (SEB) on proinflammatory cytokine/chemokine releases in primary human nasal epithelial cells (HNEC) of subjects with and without CRSwNP and the inhibitory effect of glucocorticoid on it. Methods Epithelial cells of NP and inferior turbinate (IT) were cultured serum free under stimulus of SEB, and interleukin (IL)-ajra.2009.23.32521beta, respectively. Furthermore, the inhibitory effect of glucocorticoid on the proinflammatory response was investigated by addition of dexamethasone. In situ hybridization and Western immunoblot assays were used to investigate the proinflammatory impact of SEB on IL-5 and granulocyte macrophage colony-stimulating factor (GM-CSF) mRNA levels and protein production in HNEC. Results Results indicate (1) stimulation of HNEC with SEB resulted in increased IL-5 and GM-CSF expression, which could be suppressed by dexamethasone (p < 0.05), and SEB at concentrations of 1-100 ng/mL effectively promoted IL-5 and GM-CSF release by HNEC (p < 0.05); (2) patients with CRSwNP showed a significantly increased expression of IL-5 and GM-CSF in HNEC than patients without CRSwNP (p < 0.05); and (3) the expression of IL-5 and GM-CSF was significantly up-regulated under the stimulus of SEB compared with IL-1β (p < 0.05). Conclusion SEB acts as a superantigen and exhibits a dramatic proinflammatory impact on HNEC, which can be inhibited by the addition of glucocorticoid.

Correlation analysis of two serum-specific immunoglobulin E test systems and skin-prick test in allergic rhinitis patients from northeast China.

Background Skin-prick testing (SPT) is the most common screening method for allergy evaluation. The detection of serum-specific immunoglobulin E (sIgE) is also commonly used. The sensitivity and specificity of these testing methods may vary due to type of causative allergen and type of allergic manifestation. The purpose of this study was to evaluate the correlation between two methods of measuring sIgE (AllergyScreen [Mediwiss Analytic GmbH, Moers, Germany] and ImmunoCAP [Pharmacia, Uppsala, Sweden]) and SPT for the diagnosis of allergic rhinitis (AR). Methods All 216 patients who were referred to the allergist for suspected AR from June to October 2009 had SPT and the two serological tests. One hundred fifty-eight patients had a positive clinical history and a related positive SPT. The SPT was used as reference standard, and we selected three allergens (Dermatophagoides pteronyssinus, mugwort, and ragweed), which were common in fall in northeast China, to analyze the correlation of the two serum tests and SPT. Results Compared with the SPT, the diagnostic indexes (accuracy, sensitivity and specificity) of the AllergyScreen system and the ImmunoCAP system were 0.819 versus 0.810, 0.780 versus 0.872, and 0.862 versus 0.741, respectively. The accuracy was similar between the two systems (p > 0.05). The ImmunoCAP system method had a higher sensitivity (p < 0.01). The AllergyScreen system had a higher specificity (p < 0.01). Conclusion These data support that the AllergyScreen system and ImmunoCAP system can identify potentially significant allergens in the diagnosis of AR in patients from northeastern China.

Effects of minimal persistent inflammation on nasal mucosa of experimental allergic rhinitis.

Background Minimal persistent inflammation (MPI) is considered another piece of the complex puzzle of allergic inflammation. Although some studies regarding MPI have been reported, no study has evaluated the effects of MPI on the structure changes at the site of allergic reaction. This study investigates whether long-time MPI during allergic rhinitis (AR) results in some features of tissue remodeling in the nasal mucosa. Methods An animal model of MPI was developed by repeated nasal challenge with low concentration of ovalbumin (OVA) in sensitized guinea pigs. The models were assessed by allergic symptom after antigen challenge, eosinophil infiltration in the nasal mucosa, and intercellular adhesion molecule (ICAM) 1 expression on nasal epithelial cells. The histopathological changes in nasal mucosa were determined by Alcian blue—periodic acid–Schiff and Massons trichrome staining. The expression of transforming growth factor (TGF) β1 and matrix metalloproteinase (MMP) 9 was examined by immunofluorescence under a confocal laser scan microscope. Results When sensitized animals were challenged with the low concentration of 0.01% OVA, the symptom of sneezing disappeared, but there were still mild eosinophils infiltration and weak ICAM-1 expression, which indicated the success of MPI models. Moreover, the number of goblet cells and the percentage area of collagen deposition were both mildly increased. The expression of MMP-9 and TGF-β1 was also weakly elevated. Conclusions We have successfully established MPI models and proved long-time MPI may result in mild features of remodeling in the nasal mucosa, which provide new insights into the unexpected potential effects of MPI on the structural changes.

The expression and significance of immunoglobulin free light chain in the patients with allergic rhinitis and nonallergic rhinitis.

Background Inflammation has been shown to be an integral component of allergic rhinitis (AR). However, there is no n worth debate regarding this fact in nonallergic rhinitis (NAR). Some studies have suggested that exclusion of inflammation is indicative of NAR and other studies have indicated that most of the NAR patients have some degree of inflammation. Recently, it has been shown that the level of immunoglobulin free light chains (IgFLCs) in serum is increased in some autoimmune diseases and airway inflammation. This study was designed to show whether IgFLC is associated with non–IgE-mediated rhinitis to reveal the relationship between the expression of IgFLC and activation of mast cells and eosinophils. Methods Thirty patients with IgE-mediated AR and 30 patients with NAR and 30 healthy persons as control were involved this study. The total IgE, IgFLC, eosinophil cationic protein (ECP) and mast cell tryptase (MCT) in serum, and nasal secretions were assayed, respectively. For identifying the expression cells of IgFLC in nasal mucosa, the immunohistochemical (IHC) staining for kappa-FLC, gamma-FLC, ECP, and MCT were performed on 30 specimens. Meanwhile, the mRNA expression of kappa-FLC, gamma-FLC, and MCT was determined by real-time quantitative polymerase chain reaction. Results IgFLCs (kappa/lambda) levels in serum and nasal secretion were significantly increased in AR patients and NAR patients. The ECP and MCT levels in serum and nasal secretion were significantly enhanced in AR and NAR patients when compared with healthy control subjects (p < 0.01). There was a positive correlation between IgFLC (kappa/lambda) and MCT n nasal secretion of patients with NAR, but only IgFLC (kappa-FLC was associated with MCT in AR. There was no correlation between IgFLC and ECP in nasal secretion. In serum expression level, there was a positive correlation between IgFLC (kappa) and ECP in AR or IgFLCs (lambda) and ECP in NAR. IHC staining showed that FLC+ cells were significantly increased in AR and NAR mucosa, kappa-FLC was mainly expressed in epithelial cells, and lambda-FLC was mainly expressed in subepithelial cells. Double immunofluorescence staining showed that the expression of lambda-FLC was mainly localized in mast cells in NAR nasal mucosa (45%). Conclusion These findings suggest strongly that IgFLC may play an important role in inducing local nasal mucosa inflammation especially those in AR and NAR.