Serum cytokine profiles during engraftment syndrome and acute graft-versus-host disease in adult patients after hematopoietic stem cell transplantation.

BACKGROUND: The underlying biology of engraftment syndrome (ES) following allogeneic hematopoietic stem cell transplantation (HSCT) is not fully elucidated, and the extent of its overlap with acute graft-versus-host disease (aGvHD) remains unclear. In order to establish potential indicator to distinguish ES more accurately, we conducted a retrospective analysis of cytokine levels during HSCT. METHODS: A total of 121 consecutive adult patients who underwent HSCT were enrolled in this study. Blood samples for interleukin (IL)-2, IL-2R, IL-4, IL-5, IL-6, IL-8, IL-10, IL-1ß, IL-12p70, interferon (IFN)-γ, IFN-α, tumor necrosis factor alpha (TNF-α) and C-reactive protein CRP were regularly assessed after transplantation and during transplantation related adverse events. Additionally, the balance of naïve, central memory and effector memory of CD4+ and CD8+ was analyzed around 30 and 60 days after stem cell infusion, respectively. RESULTS: Thirty (24.79 %) and 33 (27.27 %) patients were diagnosed with ES and aGvHD, respectively. ES was characterized by a significant increase in level of IL-5, IL-6, IL-8 and sIL-2R, while aGvHD was associated with a significant upregulation of IL-6, IL-5, IL-10 and sIL-2R in the patients from grade I to grade IV. Notably, patients got much higher levels of IL-6, IL-5 and sIL-2R when developed to ES than to aGvHD. Moreover, a pronounced shift from naïve to memory cells, both in CD4+ and CD8+ subsets, was found in ES patients. CONCLUSIONS: These findings suggest that cytokine profiles could serve as potential indicators for detecting and differentiating ES and aGvHD, enabling timely clinical intervention. Prospective clinical trials involving larger, independent patient cohorts are required to validate these observations.

Surfactant protein-A inhibits thymic stromal lymphopoietin-mediated T follicular helper cell differentiation and IgE production in asthma.

Lung surfactant protein A (SP-A) is critical for immunomodulation. Thymic stromal lymphopoietin (TSLP)-activated dendritic cells (DCs) drive T follicular helper (Tfh) cells differentiation in allergic asthma. We employed wild-type (WT) and SP-A-/- mice injected with TSLP and ovalbumin (OVA)-activated DCs and challenged with OVA. Compared with WT mice, we showed that allergic inflammation was dramatically increased in SP-A-/- mice. In parallel, both IL-4-producing CD45RA-CXCR5+PD-1+CD4+ cells (Tfh2) and IgE were markedly increased in SP-A-/- mice. Further study showed that SP-A prohibited TSLP activated-DCs from expressing OX40L. When we blocked OX40L-OX40 and IL-4R signaling, the differentiation of Tfh2 and IgE responses in SP-A-/- mice was significantly inhibited. In severe asthma patients, SP-A is dysfunctional in modulating the TSLP-DCs-mediated differentiation of Tfh cells. This study suggests that SP-A acts as a modulator of Tfh differentiation and IgE generation in asthma.

Inflammation accelerates copper-mediated cytotoxicity through induction of six-transmembrane epithelial antigens of prostate 4 expression.

Copper is an essential trace metal, but imbalance in copper homeostasis can induce oxidative damage. Inflammation is a fundamental element of various pulmonary diseases. Although a positive relationship between copper and chronic pulmonary diseases has been reported, the underlying reasons are still not clear. The copper level in the sputum of patients with various pulmonary diseases was measured. An inflammatory model was established to evaluate the impact of inflammation on copper uptake in the lung. We found that the level of sputum copper was increased in patients with various pulmonary diseases, especially chronic obstructive pulmonary disease and asthma. Then, we confirmed that mice with pulmonary inflammation were susceptible to copper-mediated oxidative damage because of copper overload in lung tissue. Further investigation demonstrated that interleukin (IL)-17 and tumor necrosis factor (TNF)-α exerted synergistic effects in airway epithelial cells by upregulating the expression of six-transmembrane epithelial antigens of prostate 4 (STEAP4), a metalloreductase that reduces extracellular copper ions from the cupric state to the cuprous state and facilitates copper uptake. Inhibition of STEAP4 decreased the copper uptake of cells and inhibited copper-mediated oxidative damage. Moreover, we demonstrated that the upregulation of STEAP4 by IL-17 and TNF-α was largely dependent on TNF receptor-associated factor 4 (TRAF4). Traf4-/- mice were resistant to copper-mediated oxidative damage. Our data suggest a novel IL-17/TNF-α-TRAF4-STEAP4 axis that regulates copper homeostasis.

Theoretical insights into volatile iodine adsorption onto COF-DL229.

COF-DL229 is one of the promising sorbents for the capture of volatile radioiodine due to its large adsorption capacity. However, the interaction mechanism between them remains unclear. In the present work, the adsorption of volatile iodine onto COF-DL229 was systematically investigated using periodic density functional theory and crystal orbital Hamilton population calculations. The "soft" characters of COF-DL229 have been theoretically demonstrated. Furthermore, the adsorption energies are extremely large (-8.38 to -9.26 eV), which mainly originate from the framework deformation energies, accounting for 90% at least. The I2 interacts with the skeleton mainly through the N atoms of the imine linkers or the C atoms of the phenyl rings. And, the I-N bond is the strongest bond among all the potential secondary bonds formed between the skeleton and I2. The electrons could be transferred from the skeletons to the iodine atoms and from the near iodine atom to the far one. It is also found that the energy gap becomes narrow after iodine adsorption and the skeletons mainly interact with the bonding orbital σp of I2. The present work could provide reasonable theoretical explanations to the corresponding experimental investigations and contribute to the design and screening of better sorbents for the capture of volatile radioiodine.

[IgG4-related lung disease:a clinical analysis and literature review].

OBJECTIVE: To summarize the clinical features, diagnosis and treatment experience of IgG4-related lung disease for the sake of improving clinical understanding of this disease and reducing the misdiagnosis and mistreatment rates. METHODS: To analyze the general situation, clinical manifestation, laboratory examination, histopathology, therapy and prognosis of 2 patients with IgG4-related lung disease, who were admitted in the department of respiratory diseases at Changhai Hospital. Publications related to IgG4 lung disease were reviewed. RESULTS: Both patients were male with elevated serum IgG4 level (2.25 g/L and 10 g/L respectively). In one patient, radiologic finding showed solid nodules in the lung with ileocecal involvement. He responded well to glucocorticoid. The other patient's computed tomography of lung demonstrated bronchovascular type. Glucocorticoid therapy was effective to both patients. A total of 69 cases with IgG4-related lung disease were reported worldwide, among whom 39 cases were admitted with chief complaints of respiratory symptoms. However, there were 41 cases suffering extra-pulmonary involvement. Serum IgG4 levels detected in 48 cases were significantly elevated (307-52 500 mg/L). The radiographic pattern of solid nodule type was the most frequent, accounting for 50.7% (35 cases). A total of 31 (44.9%) patients received glucocorticoid therapy with good response and prognosis. CONCLUSION: IgG4-related lung disease is a rare immunological disease lack of specific symptoms. Serum immunological examination, radiographic characteristics and histopathology should be comprehensively considered for diagnosis. Glucocorticoid is so far the most acceptable therapy with good response rate.

A regulatory role for IL-10 receptor signaling in development and B cell help of T follicular helper cells in mice.

IL -10 is widely accepted as a survival, proliferation, and differentiation factor for B cells. However, IL-10 deficiency accelerates disease progression as the result of autoantibody production in many autoimmune disease models. It was demonstrated that T follicular helper cells (T(FH) cells) play a key role in helping B cells that are secreting Abs. In this study, we demonstrated a regulatory role for IL-10R signaling on the development and B cell help function of T(FH) cells in vitro and in vivo. IL-1R subunit ß-deficient (Il10rb(-/-)) Th cells were able to differentiate more readily into T(FH) cells, as well as secrete more IL-21 and IL-17 compared with wild-type Th cell-derived T(FH) cells. Increased IL-21 and IL-17 contributed to the enhanced B cell help functions of T(FH) cells. Further experiments demonstrated that IL-6 and IL-23 from dendritic cells in Il10rb(-/-) mice contributed to the differentiation of naive Th cells into T(FH) cells, as well as the generation of IL-21- and IL-17-producing T(FH) cells. Our results provide useful information for clarifying the immunoregulatory mechanisms associated with IL-10 deficiency in certain autoimmune disease models. This information could also be of benefit for the development of vaccines.

Lipopolysaccharide mediated mast cells induce IL-10 producing regulatory T cells through the ICOSL/ICOS axis.

The mechanisms by which mast cells (MCs) regulate immune responses are still largely unknown. Here, we showed that MCs induced interleukin (IL)-10 producing T cells to regulate inflammatory responses. To gain insight into the molecules involved, we set up an in vitro system in which lipopolysaccharide (LPS) stimulated MCs and CD4(+) T cells were co-cultured. Induction of IL-10 producing regulatory T cells mainly relied on the inducible costimulator ligand (ICOSL)/ICOS axis. MCs stimulated with LPS for more than 6 weeks upregulated ICOSL expression, while icosl(-/-) BMMCs failed to induce IL-10 producing T cells. The LPS effect was mediated through NF-κB activation via the TLR4 signaling pathway. Ex vivo analysis of bronchoalveolar lavage fluid from mice with LPS-mediated pneumonia revealed ICOSL(+) MCs and IL-10 producing T cell induction. Additionally, adaptive transfer of ICOSL(+) BMMCs attenuated LPS-mediated inflammation in MC-deficient mice. This study provided new evidence for the regulatory role of MCs.

Overexpression of TRAF4 promotes lung cancer growth and EGFR-dependent phosphorylation of ERK5.

Tumor necrosis factor receptor-associated factor 4 (TRAF4) is overexpressed in a variety of carcinomas of different origins, but its role in tumorigenesis remains incompletely understood. Previous studies suggest that TRAF4 promotes epidermal growth factor receptor (EGFR) activation in non-small cell lung cancer (NSCLC). However, the downstream signaling pathway of TRAF4-mediated EGFR activation, as well as its effects on tumor cells, have not been fully elucidated. Here we report that TRAF4 overexpression is associated with increased activity of extracellular signal-regulated kinase 5 (ERK5) in NSCLC tissues. Activation of ERK5 was dependent on TRAF4-mediated EGFR activation, since inhibition of either TRAF4 or EGFR dramatically abolished phosphorylation of ERK5. Mechanistically, EGFR recruited mitogen-activated protein kinase kinase kinase 3 (MEKK3), an upstream kinase of ERK5, in a TRAF4-dependent manner. Thus, our data suggest that an EGFR-TRAF4-MEKK3-ERK5 axis promotes the proliferation of tumor cells, and this may be a potential target for therapeutic intervention of NSCLC.

Pulmonary surfactant protein D binds MD-2 through the carbohydrate recognition domain.

Pulmonary surfactant protein D (SP-D) is a member of the collectin family and plays crucial roles in the innate immunity of the lung. We have previously shown that surfactant protein A (SP-A), a homologous collectin, interacts with MD-2 and alters lipopolysaccharide signaling. In this study, we examined and characterized the binding of SP-D to MD-2 using a soluble form of recombinant MD-2 (sMD-2). SP-D bound in a concentration- and Ca(2+)-dependent manner to sMD-2 coated onto microtiter wells. Excess mannose abolished the binding of SP-D to sMD-2. In solution, SP-D cosedimented with sMD-2 in the presence of Ca(2+). The direct binding of SP-D to sMD-2 was confirmed by BIAcore analysis. Anti-SP-D monoclonal antibody that recognizes the carbohydrate recognition domain (CRD) of SP-D significantly inhibited the binding of SP-D to sMD-2, indicating the involvement of the CRD for the binding to sMD-2. Ligand blot analysis revealed that SP-D bound to N-glycopeptidase F-treated sMD-2. In addition, the biotinylated SP-D pulled down the mutant sMD-2 with Asn(26) --> Ala and Asn(114) --> Ala substitutions, which lacks the consensus for N-glycosylation. Furthermore, the sMD-2 mutant cosedimented SP-D. These results demonstrate that SP-D directly interacts with MD-2 through the CRD.

Metabolic profiling of asthma in mice and the interventional effects of SPA using liquid chromatography and Q-TOF mass spectrometry.

Asthma is a chronic inflammatory lung disease that leads to 250 000 deaths annually. There is a need to better understand asthma by identifying new pathogenic molecules. We conducted a liquid-chromatography time-of-flight mass spectrometry (LC-Q-TOF-MS)-based metabolomics study to test for asthma and investigate the interventional mechanisms of surfactant protein A (SPA) in OVA-induced asthma mice. The results revealed that asthma disturbed 32 metabolites in 9 metabolic pathways. After SPA treatment, the metabolomics profile found in asthma was significantly reversed, shifting much closer to that of the control group, indicating that SPA has therapeutic effects against asthma. Metabolomic pathway analysis by the ingenuity pathway analysis demonstrated that several pathways including fatty acid metabolism, lipid metabolism, and purine metabolism were significantly altered in asthma. This study offers new methodologies for the understanding of asthma and the mechanisms of SPA in treating asthma.

[Amiodarone pneumonitis with Hypermastigote lung infection: a case report and review of the literatures].

OBJECTIVE: To describe the clinical features of amiodarone pneumonitis with Hypermastigote lung infection. METHODS: Case report and review of the related literatures. The clinical symptoms, laboratory tests, radiographic patterns, diagnosis, and therapeutic management of amiodarone pneumonitis with Hypermastigote lung infection were described. RESULTS: A 58 year old male patient presented dyspnea after exertion. Pulmonary function showed decrease of the diffusing capacity, and CT showed interstitial changes and alveolar exudation. Foamy cells and Hypermastigotes were found in the bronchoalveolar lavage fluid. After cessation of amiodarone and the start of anti-parasite therapy, the symptoms relieved. CONCLUSIONS: Amiodarone pneumonitis with Hypermastigote lung infection is very rare. The infection may be due to decrease of local immunity caused by amiodarone pneumonitis.

Malignant pleural effusion supernatants are substitutes for metastatic pleural tumor tissues in EGFR mutation test in patients with advanced lung adenocarcinoma.

BACKGROUND: Though the possibility of using malignant pleural effusions (MPEs) as alternatives for metastatic pleural tumor tissues (MPTTs) in epidermal growth factor receptor (EGFR) mutation test has been examined, due to the lack of studies comparing the results in matching MPEs and MPTTs, the clinical value of MPEs for advanced adenocarcinoma patients with pleural effusions is not confirmed. METHODS: EGFR mutation statuses in matching MPTTs, MPE supernatants and cell blocks, of 41 patients with advanced lung adenocarcinoma as diagnosed by thoracoscopy were analyzed using amplification refractory mutation system (ARMS). RESULTS: EGFR mutations were detected in 46.3% (19/41) of MPTTs, 43.9% (18/41) of MPE supernatants and 56.3% (18/32) of MPE cell blocks by ARMS analysis. Generally, the same EGFR statuses were identified in both MPTTs and matching MPE cell blocks of 81.3% patients (26/32), whereas MPTTs and matching MPE supernatants of 87.8% (36/41) patients shared the same EGFR status. Compared with EGFR mutation detection in MPTTs, the sensitivity of EGFR mutation detection in MPE-cell blocks was 87.5% (14/16), specificity was 75.0% (12/16), while the sensitivity of EGFR mutation detection in MPE-supernatants was 84.2% (16/19), specificity was 90.9% (20/22). CONCLUSIONS: The high concordance of EGFR mutation statuses between MPEs and MPTTs in lung adenocarcinoma patients with pleural metastasis as determined by ARMS analysis suggests that MPEs, particularly MPE supernatants, may be substitutes for MPTTs in EGFR mutation test.

Predicting chemotherapy toxicity in older adults with lung cancer.

OBJECTIVE: Existing oncology performance status measurements are used to predict chemotherapy toxicity in all patients with cancer, regardless of age. A new predictive model for grade 3-5 chemotherapy toxicities was developed by Hurria et al. (2011).(1) As the model is from the Cancer and Aging Research Group (CARG), we call it the CARG toxicity tool. We investigated whether this tool can usefully characterize chemotherapy risks for older patients with lung cancer. METHODS: Patients from our hospital aged ≥ 65 years with lung cancer completed a questionnaire form prior to chemotherapy. We reviewed patients' chemotherapy courses to identify toxicities, and used the toxicity tool to score the patients' outcomes. The sample was divided into three risk strata based on approximate risk score quartiles, with the middle two quartiles combined. Chi-square statistics were used to verify differences among groups. RESULTS: Between September 2011 and September 2012, 120 patients with lung cancer (87 males and 33 females) ≥ 65 years of age (mean: 69 years; range: 65-82 years) were enrolled in the study. In our sample, 35% of subjects had ≥ one grade 3-5 hematologic toxicity; 48% had ≥ one grade 3-5 nonhematologic toxicity. Toxicity varied significantly among the risk groups (P<0.001), but the incidence of toxicity did not vary significantly among the KPS-based risk groups (P=0.322). CONCLUSION: This new CARG toxicity tool can be used to better distinguish the risks of chemotherapy toxicity than the KPS for older patients with lung cancer, and may change the standards for oncology assessments.

B and T lymphocyte attenuator is highly expressed on intrahepatic T cells during chronic HBV infection and regulates their function.

BACKGROUND: T cell antiviral function is impaired during chronic hepatitis B (CHB). Programmed death-1 (PD-1) impairs antiviral T cell responses, but dysfunction is not always reversed by blockade of PD-1 pathway. Whether distinct T cell populations expressing different sets of inhibitory molecules exist has not been determined. METHODS: We studied the expression of the B and T lymphocyte attenuator (BTLA) on both peripheral blood mononuclear cells (PBMC) and intrahepatic lymphocytes, and the effects of blocking BTLA on circulating and intrahepatic T cells in CHB patients. Sixty-three CHB patients who underwent liver biopsy were enrolled. The expression of BTLA and PD-1 on PBMC and intrahepatic T cells was assessed by flow cytometry with antibodies to T cell differentiation molecules. Functional recovery was evaluated by analyzing production of interferon (IFN)-γ and interleukin (IL)-2 after incubation of T cells with anti-CD3 and irradiated mature dendritic cells in the presence of anti-BTLA, anti-PD-1, or both. RESULTS: Intrahepatic T cells expressed higher levels of BTLA than their peripheral counterparts. A significant fraction of intrahepatic T cells coexpressed BTLA and PD-1 and showed deep exhaustion of T cell responses. Blockade of the BTLA pathway enhanced both intrahepatic and PBMC T cell proliferation and cytokine secretion, and exhibited an additive effect upon blockage of PD-1. CONCLUSIONS: Upregulation of inhibitory receptor BTLA restricts T cell responses in CHB. T cell exhaustion by high antigen concentrations exacerbates dysfunction of peripheral and intrahepatic T cells. Blockage of BTLA is a potential therapeutic approach for chronic HBV infection that may act by restoring antiviral T cell responses.

[Study on synthesis on a novel nano-antibacterial inorganic filler and its antibacterial property].

OBJECTIVE: To synthesize a novel nano-antibacterial inorganic filler and provide a new way to give dental composite resin antibacterial property. METHODS: Quaternary ammonium iodide N,N,N-trimethyl-3-(trimethoxysilyl) propan-1-aminium iodide were organically synthesized firstly and then the N,N,N-trimethyl-3-(trimethoxysilyl) propan-1-aminium iodide was grafted to the nano-silica particle to synthesize the antihacterial inorganic fillers nano-silica particle grafted with quaternary ammonium salt. All the products were analyzed and identified by infrared spectrum analysis. Then Streptococcus mutans were chosen as experimental object to analysis the antibacterial property of nanoantibacterial inorganic filler. RESULTS: Quaternary ammonium salt was grafted to the surface of nano-silica particles successfully by infrared spectrum analysis. Compared with the control group, the nano-silica particle grafted with quaternary ammonium salt had a strong bactericidal effect on Streptococcus mutons (P < 0.01). CONCLUSION: The nano-silica particle grafted with quaternary ammonium salt has a strong antibacterial property and could be used to improve dental composite resin antibacterial property.

Bronchoscopy in some tertiary grade A hospitals in China: two years' development.

BACKGROUND: Although bronchoscopy has been widely performed in China, little has been known about its current state and development. In order to investigate the clinical application of bronchoscopy and make instructions for future education and development, the Chinese Society of Respiratory Diseases conducted postal surveys in both 2008 and 2010 in China. METHOD: Questionnaires were sent to 40 tertiary grade A hospitals in 2008 and 58 tertiary grade A hospitals in 2010 to investigate bronchoscopies performed in 2007 and 2009 respectively. RESULTS: Thirty (75%) hospitals returned the completed questionnaires in 2008 and forty-one (71%) hospitals in 2010. All the respondents possessed flexible bronchoscopes. Fifty percent of the respondents had less than five in 2007, while more than 50% of the respondents had 5-9 bronchoscopes in 2009. All the respondents performed a radiograph or CT scan before bronchoscopy. Percentage of general anesthesia and no pre-medication before bronchoscopy increased, while atropine usage decreased in 2009 compared to 2007. During bronchoscopy, pulse oximetry was the most widely used monitoring method. Most respondents used the nasal route to perform routine bronchoscopy. After the procedure, they used sinks to wash and glutaraldehyde to disinfect the bronchoscopes. The total number of flexible bronchoscopies performed during 2007 was 37 874 and the average was 1262. Whereas in 2009, the total number was 60 178 and the average was 1468. Diagnostic bronchoscopy was more widely used than therapeutic bronchoscopy. The mortality rate was 0.076‰ in 2007 and 0.032‰ in 2009. CONCLUSIONS: The two surveys, to some extent, reflected the current status and development of bronchoscopy in China. The results are worthy of future education and developing of new guidelines. Regular surveys and monitoring of bronchoscopies across China are needed.

Pulmonary metastases 12 years after a mastectomy for borderline phyllodes tumor.

Phyllodes tumor is a rare breast tumor. A 45-year-old woman who underwent left mastectomy 12 years ago was found to have infiltrates in both lungs in a health examination. Combining histological examinations of the lung and breast samples, the diagnosis of borderline phyllodes tumor metastases to the lung was made. It is the longest interval to our knowledge that the metastases occurred 12 years after primary phyllodes tumor.

A new inducible adenoviral expression system that responds to inflammatory stimuli in vivo.

BACKGROUND: Gene transfer using inducible promoters, which control expression of transgenic proteins in response to physiological conditions, may have significant advantages. In this study, we tried to achieve an inducible adenoviral expression system for physiologically responsive gene therapy of autoimmune or inflammatory diseases. METHODS: A luciferase reporter vector with a hybrid promoter containing the human IL-1beta enhancer region (-3690 to - 2720) and the human CIITA promoter IV (-399 to + 2) was constructed. A replication-deficient adenovirus was engineered with luciferase controlled by the IL1beta/CIITApIV promoter (Ad-IL1beta/CIITApIV-Luc). The reporter vector or adenovirus was transfected to C57Bl/6 myeloid dendritic cells (DCs), RAW264.7, and Hep G2 to study the in vitro characteristics of this hybrid promoter. An inflammation model was prepared by injecting lipopolysaccharide (LPS) into Balb/c mice intraperitoneally (i.p.), and infected with Ad-IL1beta/CIITApIV-Luc or Ad-CMV-Luc to study the in vivo characteristics of the IL1beta/CIITApIV promoter. RESULTS: The IL1beta/CIITApIV hybrid promoter has pronounced promoter activity, broad-range responsiveness to cytokines or LPS, and can be rechallenged after first induction. In the inflammation model, IL1beta/CIITApIV could drive hepatic luciferase expression increasedly rapidly after LPS challenge and in a LPS dose-dependent manner. CONCLUSIONS: Using the IL1beta/CIITApIV hybrid promoter in gene transfer vectors may make it possible to produce transgenic proteins in vivo in direct relationship with the intensity and duration of an individual's status. By providing endogenously controlled production of transgenic proteins, this approach might limit the severity of autoimmune or inflammatory response without interfering with the beneficial components of host defense and immunity.

The effect of N-acetylcysteine on Clara cells and Clara cell 16 kDa protein in a murine model of allergen-induced airway inflammation.

OBJECTIVE: The aim of this study was to investigate the number of Clara cells and the production and secretion of Clara cell 16 kDa protein (CC16) in a murine model of allergen-induced airway inflammation, as well as the effects of N-acetylcysteine (NAC) on CC16 and Clara cell numbers, in order to determine the mechanism of the anti-inflammatory effect of NAC. METHODOLOGY: BALB/c mice were divided into control, ovalbumin (OVA) and NAC groups. An allergen-induced airway inflammation model (OVA group) was established by sensitizing and challenging mice with OVA. NAC was administered as an oral treatment. The number of Clara cells and the production of CC16 were determined by immunohistochemistry. The CC16 levels in bronchoalveolar lavage fluid (BALF) were determined by Western blotting. RESULTS: The proportion of Clara cells in terminal and respiratory bronchioles significantly decreased in the OVA group compared to the control group (P < 0.01). NAC treatment did not change the proportion of Clara cells in the OVA group (P > 0.05). CC16 production by Clara cells in the OVA groups was significantly lower than that of the control group (P < 0.01), but was elevated following NAC treatment (P < 0.05). The CC16 level in BALF of the OVA group was lower than that of the control group (P < 0.01), but was elevated by NAC treatment (P < 0.05). NAC reduced the total number of white cells and the percentage of eosinophils in BALF. Moreover, it inhibited airway inflammation. CONCLUSIONS: The number of Clara cells and the production and secretion of CC16 were reduced in a murine model of allergen-induced airway inflammation. Antioxidants can enhance the expression of CC16, which might be a mechanism by which they suppress airway inflammation.