Kai-Sheng Yin

High‐sensitivity C‐reactive protein: A predicative marker in severe asthma

Background and objective:  Serum levels of high‐sensitivity CRP (hs‐CRP) are associated with asthma but the relationship between higher levels of hs‐CRP and the degree of asthma severity remains unclear. This study investigated whether hs‐CRP is associated with asthma severity as well as with other clinical indices of asthma activity (pulmonary function, total serum IgE, and peripheral blood eosinophil counts).

Apigenin inhibits allergen-induced airway inflammation and switches immune response in a murine model of asthma

Many flavonoids were demonstrated to posses the antiallergic effect. Here we detected whether apigenin, a flavonoid, can attenuate allergen-induced airway inflammation and what is the possible mechanism in a murine model of asthma. Apigenin decreased the degree of the inflammatory cell infiltration, airway hyperresponsiveness, and total immunoglobulin E levels compared with the ovalbumin group. In addition, apigenin triggered the switching of the immune response to allergens toward a T-helper type 1 (Th1) profile. Our data clearly demonstrated that apigenin exhibits an anti-inflammatory activity in a murine asthma model, and can switch the immune response to allergens toward the Th1 profile.

IMIQUIMOD, A TOLL‐LIKE RECEPTOR 7 LIGAND, INHIBITS AIRWAY REMODELLING IN A MURINE MODEL OF CHRONIC ASTHMA

1 Imiquimod, a synthetic Toll‐like receptor (TLR) 7 ligand, has been shown to attenuate airway inflammation and airway hyperresponsiveness (AHR) in acute murine models of allergic asthma. In the present study, we investigated the effect of imiquimod on allergen‐induced airway remodelling in chronic experimental asthma. 2 Ovalbumin (OVA)‐sensitized mice were chronically challenged with aerosolized OVA for 8 weeks. Some mice were exposed to an aerosol of 0.15% imiquimod daily during the period of OVA challenge. Twenty‐four hours after the last OVA challenge, mice were evaluated for the development of airway inflammation, AHR and airway remodelling. The levels of total serum IgE and Th2 cytokines (interleukin (IL)‐4, IL‐5 and IL‐13) in bronchoalveolar lavage fluid (BALF) and the expression of transforming growth factor (TGF)‐β1 protein in lungs were measured by ELISA and immunohistochemistry, respectively. 3 The results demonstrated that imiquimod significantly inhibited chronic inflammation, persistent AHR and airway remodelling in chronic experimental asthma. In addition, imiquimod reduced levels of total serum IgE and BALF Th2 cytokines and diminished expression of TGF‐β1 in remodelled airways. 4 In summary, the results of the present study indicate that imiquimod may attenuate the progression of airway inflammation and remodelling, providing potential in the treatment of asthma.

Ligustrazine corrects Th1/Th2 and Treg/Th17 imbalance in a mouse asthma model.

Asthma is an inflammatory disease closely associated with activated T cells in the lung. Imbalances in Th1/Th2 and Treg/Th17 have been found in asthmatic patients. Ligustrazine from the Chinese herb chuanxiong has been used in China in combination with glucocorticoids to treat asthma. Previous studies have proved that ligustrazine can modulate the expression of transcription factors for Th1 (T-bet) and Th2 (Gata-3) in asthma. In the present study, ligustrazine alleviated allergic airway inflammation in a mouse asthmatic model by reducing the influx of eosinophils and neutrophils, which was mediated, at least in part, by the regulation of Th1/Th2 and Treg/Th17 via the re-balance of cytokine profiles and of ratios of transcription factors, T-bet/Gata-3 and Foxp3/RORγt, thus providing new insights into the mechanisms of action for asthma treatment with ligustrazine.

Unusual life-threatening Rosai–Dorfman disease of the trachea: role of NF-κB

Rosai–Dorfman disease (RDD) is a rare non-neoplastic histioproliferative disorder characterised by painless lymphadenopathy, low fever, high erythrocyte sedimentation rate, leucocytosis and hypergammaglobulinaemia. Overactivity of nuclear factor κB (NF-κB) is linked with inflammatory, cancerous and autoimmune diseases. The first case is described of an unusual life-threatening RDD of the trachea with no lymphadenopathy at risk of suffocation in a 39-year-old Chinese woman. A diagnosis of RDD was made following CT scans, thoracotomy and histological examination. Gel shift assay revealed an essential role for NF-κB overactivity in RDD. The patient remains well with no evidence of progression without treatment. Histological confirmation should be sought in all cases as the clinical manifestation of RDD is similar to asthma or lung carcinoma.

Targeted NF-κB inhibition of asthmatic serum-mediated human monocyte-derived dendritic cell differentiation in a transendothelial trafficking model

Transendothelial trafficking model mimics in vivo differentiation of monocytes into dendritic cells (DC). The serum from patients with systemic lupus erythematosus promotes the differentiation of monocytes into mature DC. We have shown that selective inhibition of NF-kappaB by adenoviral gene transfer of a novel mutated IkappaBalpha (AdIkappaBalphaM) in DC contributes to T cell tolerance. Here we demonstrated for the first time that asthmatic serum facilitated human monocyte-derived DC (MDDC) maturation associated with increased NF-kappaB activation in this model. Furthermore, selective blockade of NF-kappaB by AdIkappaBalphaM in MDDC led to increased apoptosis, and decreased levels of CD80, CD83, CD86, and IL-12 p70 but not IL-10 in asthmatic serum-stimulated MDDC, accompanied by reduced proliferation of T cells. These results suggest that AdIkappaBalphaM-transferred MDDC are at a more immature stage which is beneficial to augment the immune tolerance in asthma.

Inhibition of interleukin‐13 gene expression by triptolide in activated T lymphocytes

Triptolide, a type of diterpenoid, is the active compound of Tripterygium wilfordii; it plays roles in anti‐inflammatory and immune response regulation. Our objective was to investigate the mechanism of the inhibitory effect of triptolide on interleukin‐13 (IL‐13) gene expression in activated T lymphocytes. Understanding the molecular mechanism by which triptolide exerts a therapeutic function may be useful in developing a pharmaceutical treatment for asthma.

Hesperetin inhibits the maturation and function of monocyte-derived dendritic cells from patients with asthma.

Dendritic cells (DCs) are crucial regulators of allergic diseases. Hesperetin, an important bioactive compound in Chinese traditional medicine, has antioxidant and anti-allergic properties. In this study, we examined whether hesperetin influences surface molecule expression, cytokine production, the capacity to induce T cell proliferation, and the underlying signaling pathway in monocyte-derived DCs from patients with allergic asthma. The results show that hesperetin significantly suppressed Der p 1-induced HLA-DR, CD86 and CD83 expression in DCs. However, the secretion of IL-10 was not affected. Hesperetin-treated DCs exhibited a reduced ability to stimulate autologous CD4+ T cells, accompanied by less Th2 polarization. In addition, the Der p 1-induced phosphorylation of IκBα and the translocation of NF-κB p65 were inhibited in the presence of hesperetin. These novel findings provide insight into the immunopharmacological role of hesperetin in DC-based allergic diseases.

Polymorphisms of TLR7 and TLR8 associated with risk of asthma and asthma-related phenotypes in a southeastern Chinese Han population

Abstract Objective To evaluate the effects of polymorphisms in TLR7 and TLR8(as potential candidate genes) on asthma risk and asthma-related phenotypes. Methods We consecutively recruited 318 unrelated adult asthmatic patients and 352 healthy volunteers from the same area of southeast China. Genotyping of each selected SNP was performed using multiplex PCR in conjunction with tagged array single base extension technology. We conducted case-control and case-only association studies between the selected SNPs in TLR7 and TLR8 and asthma or asthma-related phenotypes. Results The T allele of rs5935436 SNP in TLR7 was protective from developing asthma in males (adjusted ORs = 0.126, 95% CIs = 0.016-0.995). The CT/TT genotype of rs5935436 was less frequent in female asthmatics with allergic rhinitis (adjusted ORs = 0.18, 95% CIs = 0.04-0.90). The homozygote AA of rs3761623 and GG of rs3764880 were positively associated with lower FEV1% and asthma severity in female asthmatics. These results were confirmed by haplotype analysis. Conclusion TLR7 and TLR8 polymorphisms may play an important role in the pathogenesis of asthma that is gender-dependent. This could be clinically useful, both for identifying patients at risk of asthma and for preventing its occurrence.

Respiratory syncytial virus infection differentiates airway dysfunction in the central and peripheral airways in OVA-sensitized mice

ABSTRACT Much evidence suggests that respiratory syncytial virus (RSV) infection prolongs airway hyperresponsiveness (AHR) and exacerbates asthma by enhancing airway inflammation. However, the characteristic of airway inflammation and kinetics of airway dysfunction occurred in the central and peripheral airways were not fully delineated. The objective of this study was to investigate the effect of RSV on the allergic airway inflammation in different size airways and to elucidate its possible mechanism. Using a murine model of prior ovalbumin (OVA) sensitization and subsequent RSV challenge, lung resistance (RL), and dynamic compliance (Cdyn) was conducted by barometric whole-body plethysmography. Histological examinations were carried out. Differential cells count in bronchoalveolar lavage (BAL) fluid, serum anti-OVA IgE, and IgG1 were measured. Cytokine mRNA expression in lung tissue were determined. RSV triggered a significant increase in RL and reduction in Cdyn, as well as greatly prolonged the recovery of Cdyn more than that of RL in OVA-sensitized mice. Also, RSV resulted in more severe peripheral airway inflammation which exhibit as globe cell hyperplasia and CD8+ T cell infiltration. Furthermore, the number of lymphocytes, neutrophils and macrophages in BAL fluid, serum anti-OVA IgE and IgG1 were remarkably increased. Additionally, mice increased relative expression of cytokines IL-4, IL-13, and IFN-γ, but not IL-5, IL-17, and IL-17F. These findings demonstrated that RSV could selectively affect pathologic processes that contribute to altered airway function in the central and peripheral airways in OVA-sensitized mice. These processes may be involved in goblet cell hyperplasia and CD8+ T cell infiltration in peripheral airways.