Lin-Fu Zhou

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).

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.

Regulation of Th1/Th2 balance through OX40/OX40L signalling by glycyrrhizic acid in a murine model of asthma

Glycyrrhizic acid (GA) has been reported to have attenuating airway inflammation effects in asthma mouse model. However, the potential molecular mechanisms by which GA exerts anti‐inflammatory effects on ovalbumin (OVA)‐induced allergic asthma have not been well elaborated.

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.

Effects of adenoviral gene transfer of mutated IkappaBalpha, a novel inhibitor of NF-kappaB, on human monocyte-derived dendritic cells

AbstractAim:To investigate the effects of adenoviral gene transfer of IκBα mutant (IκBαM), a novel inhibitor of nuclear factor κB (NF-κB), on apoptosis, phenotype and function of human monocyte-derived dendritic cells (DC).Methods:Monocytes, cocultured with granulocyte/macrophage colony-stimulating factor (GM-CSF; 900 ng/mL) and interleukin (IL)-4 (300 ng/mL) for 5 d, followed by stimulation with lipopolysaccharide (LPS; 100 ng/mL) for 2 d differentiated into mature DC. Monocytes were either left untransfected or were transfected with AdIκBαM or AdLacZ. The transcription and expression of the IκBαM gene, and the inhibitory effect of IκBαM on tumor necrosis factor (TNF)-α-induced NF-κB activation in mature DC were detected by polymerase chain reaction (PCR), reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis, and electrophoretic mobility shift assays, respectively. The phenotype, apoptosis, IL-12 secretion level of DC, and ability to stimulate the proliferation of T cells were determined by flow cytometry, enzyme-linked immunosorbent assay and mixed leukocyte reaction.Results:PCR and RT-PCR were used to detect a unique 801 bp band in AdIκBαM-transfected mature DC, and also a dose- and time-dependent expression of the IκBαM gene, which peaked at a multiplicity of infection of 100 pfu/cell and at 48 h. Furthermore, AdIκBαM significantly suppressed the TNF-α-induced NF-κB activation, augmented apoptosis, downregulated CD80, CD83, and CD86 surface molecules, IL-12 secretion levels and the ability to stimulate the proliferation of T cells in mature DC.Conclusion:AdIκBαM effectively transfected and potently inhibited NF-κB activation in monocyte-derived mature DC. Overexpression of the IκBαM gene in mature DC may contribute to T-cell immunosuppression through induction of DC apoptosis and downregulation of B7 molecules, providing a potential strategy for future DC-based immunotherapy of asthma.

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.

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.

[Resection of tracheal hamartoma by eletrocautery and cryotherapy via bronchoscopy under laryngeal mask anaesthesis: report of 2 cases and review of the literature].

Resection of Tracheal Hamartoma by Eletrocautery and Cryotherapy via Bronchoscopy under Laryngeal Mask Anaesthesis: Report of 2 Cases and Review of the Literature Jiwang WANG, Mao HUANG, Xu QI, Meimei LI, Linfu ZHOU, Kaisheng YIN Department of Respiratory Medicine, the First Affilliated Hospital, Nanjing Medical University, Nanjing 210029, China Corresponding author: Jiwang WANG, E-mail: Wangjiwang@yahoo.com.cn DOI: 10.3779/j.issn.1009-3419.2011.02.14

A Unique Life-Threatening Mediastinal Liposarcoma Mimicking Pleural Effusion

A 38-year-old woman with schizophrenia reported progressive dyspnea. Arterial blood gases showed type 2 respiratory failure. Her chest X-ray suggested a complete right pleural effusion (Figure 1A). Enhanced chest computed tomography revealed a unique giant encapsulated mass with adipose tissue (Figure 1B, arch arrow) and atelectasis (asterisk), indicative of liposarcoma or teratoma. A diagnosis of well-differentiated and myxoid mediastinal liposarcoma was confirmed following thoracotomy (Figures E1 and E2 in the online supplement). The presence of a mutation within PIK3CA is associated with a shortened survival (1). Strikingly, sequencing of PIK3CA identified three novel point mutations (Figure 2, upper panel ) and a frameshift mutation (lower panel) at exon 10. Kinome profiling of myxoid liposarcoma demonstrates nuclear factor-kB and Src to be the two most active pathways (2, 3). Combining technologies will allow for efficient clinical translation (4). Intrathoracic liposarcoma, although extremely rare, should be included in the differential diagnosis of pleural effusion.