The effects of long-term exposure to silica dust on serum CC16 and KL-6 levels / 中华劳动卫生职业病杂志

Objective@#To investigate the effects of long-term exposure to silica dust on serum CC16 and KL-6 levels.@*Methods@#The patients with stage I silicosis who were hospitalized in our hospital from April 2016 to April 2017 were treated as silicosis group. The silica dust exposed workers without silicosis who were taken the physical examination in our hospital were taken as a dust-exposed group. The healthy control group comes from in the same period of community physical examination did not touch the dust. The levels of CC16 and KL-6 in serum of all subjects were determined by enzyme-linked immunosorbent assay (ELISA) , and the levels of CC16 and KL-6 in serum were compared in three groups.@*Results@#Compared with the control group, the serum levels of CC16 in the silicosis group (P<0.01) and the dust-exposed group (P<0.01) were significantly lower. Compared with the control group, the level of serum KL-6 in the silicosis group was significantly decreased (P<0.01) compared with the control group, while the level of KL-6 in the serum of the dust-exposed group was significantly increased (P<0.01) . The ROC area of CC16 for diagnosis of silicosis was 0.92 (P<0.01) , with a sensitivity of 81.37%, specificity of 92.63% and Kappa value of 0.74.@*Conclusion@#Long-term exposure to silica dust may lead to a decrease in serum CC16 levels. Reduced serum CC16 levels may be useful in identifying the diagnosis of silicosis.

The expression and significance of protein AQP5 and CC16 in lung injury after hemorrhagic shock resuscitation in rats / 中华急诊医学杂志

Objective To observe the expression of protein AQP5 and CC16 in lung after hemorrhagic shock resuscitation in rats in order to explore the mechanism of acute lung injury.Methods Thirty-two healthy and clean male SD rats were randomly (random number) divided into two groups:control group and hemorrhagic shock resuscitation group (n =16 in each).Besides,each group was further divided into two subgroups according to the experiment done at 12 h and 24 h after hemorrhagic shock resuscitation (n =8).The hemorrhagic shock model was made by using Wiggers' modified method.Resuscitation was done by transfusing the autologous blood and the equal volume of Ringer's solution.Blood samples were obtained from abdominal aorta at each given interval to measure the level of plasma endotoxin,and assay the CC16 and AQP5 by using ELISA.After the rats were sacrificed,the left lung tissue was taken to measure lung water content and the dry/wet ratio,and to examine the levels of CC16 and AQP5 in lung tissue by immunohistochemical method.Results ①The level of plasma endotoxin in the experimental group was significantly higher than that in the control group (P ＜ 0.01).②The content of plasma CC16 in the experimental group was higher than that in the control group (P ＜ 0.05).③Compared with the control group,the content of pulmonary homogenate AQP5 in the experimental group was significantly lower (P ＜0.05).④The lung water content (the dry/wet ratio) of the experimental group was obviously higher than that of the control group (P ＜ 0.05).⑤Hislogogical observation with HE staining showed in the control group,the alveolar structure was complete,the alveolar sacs were clear,and the alveolar septum was intact;but in the experimental group,the alveolar septum was widened,and there were obvious hemorrhage and neutrophil infiltration in the alveolar space.⑥ The level of lung tissue CC16 in control group was significantly higher compared with experimental group (P ＜ 0.05).⑦ The level of lung tissue AQP5 was significantly higher in control group compared with experimental group (P ＜ 0.05).Conclusions The proteins of AQP5 and CC16 were involved in the process of acute lung injury after hemorrhagic shock resuscitation in rats,and their levels were positively correlated with length of time after hemorrhagic shock.

Serum Clara cell 16-kDa protein levels and lung impairment in systemic sclerosis patients / Níveis séricos de proteína de células de Clara de 16 kDa e comprometimento pulmonar em pacientes com esclerose sistêmica

ABSTRACT Objective: To assess clinical utility of serum Clara cell 16-kDa protein measurements in relation with staging system for systemic sclerosis associated interstitial lung disease. Materials and methods: Serum levels of Clara cell 16-kDa protein were determined by ELISA in 28 systemic sclerosis patients and 30 healthy controls, and correlated with staging system for systemic sclerosis associated interstitial lung disease in systemic sclerosis patients. Lung involvement was assessed functionally (body plethysmography, diffusing capacity of the lung for carbon monoxide) and radiologically (an average disease extent on high resolution computed tomography of the lungs) in SSc patients. Results: We observed statistically significant differences in serum Clara cell 16-kDa protein levels between systemic sclerosis patients and healthy controls only in non-smokers. However, serum Clara cell 16-kDa protein concentrations were significantly elevated in patients with high resolution computed tomography extent >20% in comparison to patients with high resolution computed tomography extent <20% (p = 0.01). They correlated positively with average disease extent on high resolution computed tomography (p = 0.04), an extent of a reticular pattern on high resolution computed tomography (p < 0.01), and negatively with a total lung capacity (p = 0.03) and the results of the 6-min walk test (p < 0.01). Conclusions: Clara cell 16-kDa protein levels can be considered as a supplemental serum biomarker for systemic sclerosis associated interstitial lung disease.

RESUMO Objetivo: Avaliar a utilidade clínica das medições séricas da proteína de células de Clara de 16-kDa (CC16) em relação ao sistema de estadiamento para doença pulmonar intersticial associada a esclerose sistêmica (DPI-ES). Materiais e métodos: Foram determinados os níveis séricos de CC16 por ELISA em 28 pacientes com ES e 30 controles saudáveis e correlacionados com o sistema de estadiamento para DPI-ES em pacientes com ES. O envolvimento pulmonar foi avaliado funcionalmente (pletismografia corporal, capacidade de difusão de monóxido de carbono) e radiologicamente (extensão média da doença na tomografia computadorizada de alta resolução dos pulmões, TCAR) em pacientes com ES. Resultados: Foram encontradas diferenças estatisticamente significativas nos níveis séricos de CC16 entre pacientes com ES e controles saudáveis apenas em não tabagistas. No entanto, as concentrações séricas de CC16 eram significativamente elevadas em pacientes com extensão > 20% na TCAR em comparação com pacientes com extensão < 20% na TCAR (p = 0,01). Os níveis séricos de CC16 se correlacionaram positivamente com a extensão média da doença na TCAR (p = 0,04) e com a extensão de padrão reticular na TCAR (p < 0,01) e negativamente com a capacidade pulmonar total (CPT) (p = 0,03) e com os resultados do teste de caminhada de seis minutos (p < 0,01). Conclusões: Os níveis de CC16 podem ser considerados como biomarcadores séricos suplementares para a DPI-ES.

Effect of recombinant rat CC16 protein on LPS-induced expression of TNF-α, IL-6 and IL-8 in rat tracheal epithelial cells / 中国病理生理杂志

AIM:To explore the effect of recombinamt rat CC16 protein (rCC16) on LPS-induced expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and IL-8 in the rat tracheal epithelial (RTE) cells. METHODS:The RTE cells were incubated with rCC16 at concentrations of 0.5, 1.0 and 2.0 mg/L in serum-free media for 2 h prior to LPS (0.1 mg/L) treatment for further 24 h.The cells were harvested for assessing the mRNA levels of TNF-α, IL-6 and IL-8 by RT-qPCR.The cell culture supernatants were collected for analyzing the protein levels of TNF -α, IL-6 and IL-8 by ELISA.In addition, the nuclear translocation of nuclear factor-κB (NF-κB) p65 was tested by Western blot.RESULTS:rCC16 inhibited LPS-induced IL-6 and IL-8 expression at both mRNA and protein levels in the RTE cells in a concentration-dependent (0~2 mg/L) manner, as demonstrated by RT-qPCR and ELISA.However, no concentra-tion-dependent manner between the dose of rCC 16 and TNF-αexpression was observed , and rCC16 inhibited LPS-induced TNF-αexpression at lower concentration (0.5 mg/L).rCC16 concentration-dependently inhibited the effects of LPS on the level of nuclear translocation of NF-κB p65.CONCLUSION:rCC16 suppresses LPS-mediated TNF-α, IL-6 and IL-8 pro-duction through inactivation of NF-κB activity in RTE cells .

Neutrophil predominance in induced sputum from asthmatic patients: Therapeutic implications and role of clara cell 16-KD protein / Predominio de neutrófilos en esputo inducido de asmáticos: Implicancias terapéuticas y rol de la proteína 16-kD de la célula clara

Eosinophil is considered to be a main protagonist in asthma; however, often discordances between clinical manifestations and response to treatment are observed. We aimed to determine the occurrence of neutrophil predominance in asthma and to identify its characteristics on the basis of clinical-functional features, induced sputum cellular pattern and soluble molecules, to guide the appropriated anti-inflammatory therapy. A total of 41 patients were included in randomized groups: 21-40 year-old, with stable mild-to-severe asthma, steroid-naïve and non-smokers. An induced sputum sample was obtained under basal conditions, a second one after treatment with budesonide (400 µg b.i.d.) or montelukast (10 mg/d) for six weeks, and a final one after a 4-week washout period. By cytospin we evaluated eosinophil (EP) or neutrophil predominance (NP), and in supernatant we determined LTE4, and CC16. Peak expiratory flow variability (PEFV) was measured. A total of 23/41 patients corresponded to EP and 18/41 patients to NP. The PEFV was higher in EP than in NP. LTE4 was higher with NP than with EP. No difference was found for CC16. Montelukast reduced the predominant cell in both subsets, whereas budesonide only reduced eosinophils in EP. Budesonide and montelukast reduced PEFV in EP but not in NP. Considering the total treated-samples in each subset, CC16 level increased significantly in EP. In conclusion: a NP subset of asthmatic patients was identified. These patients show a lower bronchial lability; the leukotriene pathway is involved which responds to anti-leukotriene treatment. This phenotype shows a poor recovery of CC16 level after treatment.

El eosinófilo es considerado la célula protagonista principal en el asma; sin embargo, a menudo se observan discordancias entre las manifestaciones clínicas y la respuesta de los pacientes al tratamiento. Nos propusimos determinar la ocurrencia de predominio de neutrófilos en el asma e identificar las características clínico-funcionales, el patrón celular y las moléculas solubles del esputo inducido, para guiar el tratamiento apropiado anti-inflamatorio. Se incluyeron 41 pacientes: 21 a 40 años de edad, con asma estable leve a grave, no tratados con esteroides tópicos ni sistémicos y no fumadores. Se obtuvo una muestra de esputo inducido en condiciones basales, una segunda muestra después del tratamiento al azar con budesonida (400 µg dos veces al día) o el montelukast (10 mg/d) durante seis semanas, y una final después de un período de lavado de 4 semanas. En el frotis por citocentrifugado se evaluó el predominio de eosinófilos (EP) o neutrófilos (NP), y en el sobrenadante se determinó LTE4, y CC16. Se midió la variabilidad del flujo espiratorio máximo (PEFV). Un total de 23/41 pacientes correspondieron al EP y 18/41 pacientes con NP. El PEFV fue mayor en el EP que en NP. LTE4 fue mayor en NP que en EP. No se encontraron diferencias de los niveles de CC16 en ambos grupos. Montelukast redujo la célula predominante en ambos subgrupos, mientras que budesonida sólo redujo los eosinófilos en EP. Tanto budesonida como montelukast redujeron PEFV en EP, pero no en NP. El nivel de CC16 aumentó significativamente en el EP luego del tratamiento antiinflamatorio. En conclusión: se identificó un subgrupo de asmáticos NP que presentan una menor labilidad bronquial, la vía de los leucotrienos parece estar involucrada y responde al tratamiento anti-leucotrienos. Este fenotipo muestra una escasa recuperación del nivel de CC16 posterior al tratamiento.

Effects of N-acetylcysteine on Clara cell and Clara cell16000protein in murine asthma model / 第二军医大学学报

Objective:To investigate the effects of N-acetylcysteine(NAC)on the number of Clara cells and secretion of Clara cell16000(CC16)protein in murine asthmatic model.Methods:The murine asthmatic model was established by sensitiz-ing and challenging BALB/c mice with ovalbumin(OVA).Thirty mice were divided into control,asthmatic and NAC groups (n=10). The number of Clara cells and synthesis of CC16were determined by immunohistochemistry.The CC16level in bronchoalveolar lavage fluid(BALF)was determined by Western blot.Results:The proportions of Clara cells in terminal and respiratory bronchioles were(58.05?3.75)%and(63.70?1.79)%in the asthmatic group,(74.54?5.81)%and (78.46?1.68)% in the control(P

Regulation on the expression of CC16 in acute lung injury rats’ lung by growth hormone / 中国免疫学杂志

Objective:To study the effect of growth hormone(GH) on acute lung injury induced by endotoximia and its’ mechanism.Methods:After introduction of acute lung injury(ALI) by endotoximia,one hundred and tweleve male Sprague-Dawley rats were randomly divided into ALI group and GH group. Western blot,immunofluorescence staining and semi-quantitive reverse transcription polymerase chain reaction(RT-PCR) were used to determine the expression and activation of nuclear factor kappa B(NF-?B), the levels of CC16 protein and the expression levels of CC16 mRNA in ALI rats’ lung.Results:Both the expression levels of CC16 mRNA and the contents of CC16 protein in ALI rats’ lungs began to decrease significantly 0.5 h post-injury,reached nadir at 6 h post-injury,and then began to recover.Both the expression levels of CC16 mRNA and the contents of CC16 protein in GH group were significantly lower than those in ALI group at different time intervals post-injury.The dynamic changes of the expression and activation of NF-?B were contrast to those of CC16 protein levels.Correlation analysis indicated that CC16 correlates significantly with the extent of lung injury and the expression and activation of NF-?B.Conclusion:Down-regulation of CC16 expression plays a critical role in the pathogenesis of acute lung injury induced by endotoximia.The application of GH can deteriorate the lung injury induced by endotoximia through down-regulating the expression of CC16.