Huabin Li

Induction of IL-6 and IL-8 by House Dust Mite Allergen Der p1 in Cultured Human Nasal Epithelial Cells Is Associated with PAR/PI3K/NFĸB Signaling

Objective: The mechanism of action involved in how Dermatophagoides pteronyssinus (Der p) 1 initiates the nasal allergic cascade is poorly understood. Methods: We detected proinflammatory cytokine production (GM-CSF, TNF-α, IL-1β, IL-6, and IL-8) and associated signal molecules in primarily cultured nasal epithelial cells (NECs) from patients with allergic rhinitis (AR) after Der p1 stimulation, using ELISA, RT-PCR, and Western blot. We also evaluated the importance of protease-activated receptors (PAR)/phosphatidylinositol 3 kinase (PI3K)/NFĸB signaling pathways in IL-6 and IL-8 production using glucocorticoids and specific inhibitors, LY294002 and PDTC. Results: We observed significantly elevated IL-6 and IL-8 production (both gene and protein) in NECs after Der p1 stimulation, and demonstrated that the expressions of PAR2, pAkt, and pp65 were upregulated afterDer p1 stimulation, which were associated with IL-6 and IL-8 production in NECs. Conclusion: These findings demonstrate that the PAR/PI3K/NFĸB signaling pathway is involved in the induction of IL-6 and IL-8 in Der-p1-stimulated NECs from AR patients, and may have potential implications for the prevention and treatment of AR and asthma.

Interleukin-6 is essential for Staphylococcal exotoxin B-induced T regulatory cell insufficiency in nasal polyps

Background The pathogenesis of nasal polyps is still unclear. There is increasing evidence indicating that Staphylococcal aureus (S. aureus) is associated with the formation of nasal polyps, but the mechanism has not been well documented to date.

Overproduction of Cyclin D1 is dependent on activated mTORC1 signal in nasopharyngeal carcinoma: Implication for therapy

Activated mTOR was implicated to play a role in the carcinogenesis of nasopharyngeal carcinoma (NPC). However, the mechanism of activated mTOR/Complex1(mTORC1) signaling pathway in NPC development has not been well established. In this study, we correlated the expression of mTORC1 signal molecules and Cyclin D1 in NPC. We also investigated the effect of blocking mTORC1 signal with rapamycin and mTOR siRNA on Cyclin D1 expression in CNE-2 cells, as well as cell apoptosis and viability. We found a positive association of mTORC1 signal molecules and Cyclin D1 in NPC. Also, we found blockage mTORC1 inhibited Cyclin D1 expression in CNE-2 cells and enhanced cell apoptosis. Our results suggested that mTORC1 signal pathway might be a potential target for NPC therapy.

Expression of T-cell immunoglobulin- and mucin-domain-containing molecule-1 (TIM-1) is increased in a mouse model of asthma and relationship to GATA-3.

It has been suggested that T-cell immunoglobulin-and mucin-domain-containing molecule-1 (TIM-1) plays an important role in the development of allergic asthma, though its molecular mechanism remains unclear. Our aim was to examine the expression of TIM-1 and Th2-associated transcription factor GATA-3 in asthmatic mice, and to evaluate the correlation of TIM-1 and GATA-3 in the pathogenesis of allergic asthma. We examined TIM-1 expression in lung tissue and peripheral blood mononuclear cells (PBMCs) of asthmatic mice by real-time PCR and flow cytometry, respectively; we also investigated TIM-1 and GATA-3 expression in the spleen tissue of asthmatic mice by western blot. These results demonstrate that TIM-1 was significantly increased in pulmonary tissues and PBMCs in asthmatic mice after ovalbumin (OVA) challenge (P<0.05), and that the production of TIM-1 as well as GATA-3 was upregulated in the spleen of asthmatic mice. The production of TIM-1 correlated significantly with the production of GATA-3 in the spleen of asthmatic mice (r=0.753, P<0.05). The results of this study provide the first evidence that increased expression of TIM-1 in asthmatic mice is associated with the Th2-associated transcription factor GATA-3. The findings suggest a possible mechanism for how HAV infection and TIM-1 upregulation influence the development of allergic asthma.

The antimicrobial protein short palate, lung, and nasal epithelium clone 1 (SPLUNC1) is differentially modulated in eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyps

BACKGROUND Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease with aberrant host defense responses. However, whether innate immunity is similarly impaired in patients with eosinophilic and those with noneosinophilic CRSwNP remains unclear. OBJECTIVES We sought to evaluate the expression and possible modulation of short palate, lung, and nasal epithelium clone 1 (SPLUNC1), an innate immune molecule, in the 2 CRSwNP subsets. METHODS Polyp tissue and uncinate processes were collected from 40 patients with CRSwNP, 27 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 22 control subjects. Expression of SPLUNC1; Toll-like receptor (TLR) 2, TLR3, and TLR4; and the proinflammatory cytokines IL-1α, IL-4, IL-13, IL-17A, and IFN-γ was examined in nasal tissues. Additionally, SPLUNC1 expression in response to specific inflammatory stimulation was measured in cultured polyp epithelial cells and A549 cells. RESULTS Polyp tissues exhibited significantly decreased expression of SPLUNC1 and other innate immune molecules compared with uncinate process tissues from patients with CRSwNP (P < .05), patients with CRSsNP, and healthy control subjects. Moreover, the eosinophilic CRSwNP subset exhibited significantly decreased SPLUNC1 expression and numbers of submucosal glands, as well as significantly increased IL-4 and IL-13 mRNA levels, compared with the noneosinophilic subset (P < .05). Accordingly, SPLUNC1 expression in polyp epithelial cells was significantly inhibited by IL-4 and IL-13 stimulation in vitro but was significantly upregulated after stimulation with TLR agonists and glucocorticoids (P < .05). CONCLUSION Differential SPLUNC1 suppression between the eosinophilic and noneosinophilic CRSwNP subsets suggests that they possess distinct pathogenic mechanisms. This finding might benefit the design of appropriate therapeutic interventions targeted to each subset.

Elevated serum osteopontin level is associated with blood eosinophilia and asthma comorbidity in patients with allergic rhinitis.

From the Division of Immunology, Children’s Hospital, Boston, Mass; the Department of Pediatrics, Harvard Medical School, Boston, Mass; the Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon; the Unit e de G en etique M edicale, Universit e Saint Joseph, Beirut, Lebanon; the CNRS-Institut de G en etique Humaine et Universit e Montpellier 2, Montpellier, France; the Division of Pediatric Hematology and Oncology, Children’s Center for Cancer and Blood Diseases, Rafik Hariri University Hospital, Beirut, Lebanon; and the Department of Pediatrics, ‘‘Angelo Nocivelli’’ Institute for Molecular Medicine, University of Brescia, Brescia, Italy. E-mail: raif.geha@childrens.harvard.edu. *These authors contributed equally to this work. This study was supported by USPHS grants 1P01AI076210-01A1 (to R.S.G. and L.D.N.) and T32AI007512 (to R.S.G. and J.C.), a grant from the Dubai Harvard Foundation for Medical Research (R.S.G.), and a grant provided by the Jeffrey Modell Foundation (to L.D.N.). Disclosure of potential conflict of interest: J. Chou received research support from the National Institutes of Health (NIH). L. D. Notarangelo received research support from the NIAID-NIH and the Jeffrey Modell Foundation. R. Geha received research support from the NIH and the Jeffrey Modell Foundation. The rest of the authors declare that they have no relevant conflicts of interest.

Aspirin-exacerbated respiratory disease in China: a cohort investigation and literature review.

Background Although the prevalence of aspirin-exacerbated respiratory disease (AERD) in western populations is high, AERD is rather rare in China, and few related studies have been published to date. Methods We performed a prospective cohort investigation on the incidence of AERD in patients with chronic rhinosinusitis (CRS) in southern China. A literature search of the China Academic Journal Network Publishing Database was conducted to obtain an overview of the incidence of AERD in the Chinese population, and previous studies on the incidence of AERD were reviewed. Results We found 2 patients with aspirin hypersensitivity among 351 consecutive CRS (309 with nasal polyps [NPs]) patients, suggesting a rate of 0.57% in the CRS population. Forty-five articles about AERD were obtained by Chinese-language literature searches. In total, 346 cases of AERD were reported during the past 30 years. Conclusion Given the large population of NPs in China, the prevalence of AERD is very low, and this may be related to the reduced levels of nasal tissue eosinophilia and subsequent low asthma comorbidity.

Increased IL‐21 expression in chronic rhinosinusitis with nasalpolyps

IL‐21 is a key cytokine for regulating B cell immunity, which is involved in several inflammatory conditions. This study sought to define a role for IL‐21 in activated B lymphocytes and enhanced tissue eosinophilia in NP tissues during the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP).

Broncho-Vaxom Attenuates Allergic Airway Inflammation by Restoring GSK3β-Related T Regulatory Cell Insufficiency

Background Oral administration of bacterial extracts (eg, Broncho-Vaxom (BV)) has been proposed to attenuate asthma through modulating Treg cells. However, the underlying mechanism has not been fully characterized. This study sought to assess the effects of oral administration of BV on GSK-3β expression and Treg cells in ovalbumin (OVA)-induced asthmatic mice models. Method Asthmatic mice models were established with OVA challenge and treated with oral administration of BV. Next, infiltration of inflammatory cells including eosinophil and neutrophils, mucous metaplasia, levels of Th1/Th2/Treg-typed cytokines and expression of GSK3β and Foxp3 were examined in asthmatic mice models by histological analysis, Bio-Plex and western blot, respectively. Moreover, the frequencies of Treg cells were evaluated in cultured splenocytes by flow cytometry in the presence of BV or GSK3β siRNA interference. Results We found significant decrease of infiltrated inflammatory cells in bronchoalveolar lavage fluid (BALF) in asthmatic mice models after oral administration of BV. Oral administration of BV was shown to significantly suppress mucus metaplasia, Th2-typed cytokine levels and GSK3β expression while increasing Foxp3 production in asthmatic mice models. Moreover, BV significantly enhanced GSK3β-related expansion of Treg cells in cultured spleen cells in vitro. Conclusion Our findings provide evidence that oral administration of BV is capable of attenuating airway inflammation in asthmatic mice models, which may be associated with GSK3β-related expansion of Treg cells.

The elevated expression of osteopontin and vascular endothelial growth factor in sinonasal inverted papilloma and its relationship with clinical severity.

Background Osteopontin (OPN) is involved in cell survival, immunity, and tumor progression. The overexpression of OPN has been proposed as a biomarker of progression and metastasis for several tumor types, but it is still unclear whether it is up-regulated in sinonasal inverted papilloma (SIP). Methods We enrolled 33 subjects with SIP and 15 normal controls to determine the importance of OPN and vascular endothelial growth factor (VEGF) in SIP. Using immunohistochemistry, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay, we examined the distribution, mRNA expression, and protein levels, respectively, of OPN and VEGF. We then correlated these values with clinical severity. Results The immunostaining levels for OPN and VEGF were significantly increased in SIP tissues compared with control tissues (p < 0.05), as were their mRNA expression and protein levels (p < 0.05). The correlation between OPN and VEGF expression and the clinical stage of SIP was significant (p < 0.05). Conclusion Our findings indicate that OPN and VEGF were both overexpressed in the analyzed SIP tissues and were associated with clinical severity, suggesting that the OPN–VEGF axis might contribute to tumor progression by enhancing angiogenesis. Therefore, OPN may serve as a potential therapeutic target for preventing SIP progression and recurrence.