肠上皮细胞在炎症性肠病中的作用

肠表面上皮细胞(IEC)一直被认为是肠腔内容物进入肠道的有效屏障,具有维持水电解质平衡,参与营养物质、维生素和矿物质吸收的功能.在炎症性肠病(IBD)时,IEC的这些作用出现异常.IEC还参与了肠黏膜先天性和获得性免疫应答,促进IBD的炎性反应进程.在许多IBD动物模型中均发现其原发性缺陷位于肠上皮层,并出现肠黏膜通透性缺陷.同样,IBD患者中有近10%/5的一级亲属中也出现相似的肠黏膜通透性缺陷.这些发现提示IBD患者肠上皮功能缺损有遗传因素的参与.     

微粒在慢性气道炎症性疾病中的作用

研究表明微粒作为细胞间信号转导的载体,在多种疾病中起着重要作用。它通过对细胞的内分泌、分子信号转导、物质合成等生物功能的调节而影响组织的损伤、修复,参与疾病的发生、发展。在病理状态下,微粒数量增多、内容物发生改变,影响靶细胞的物质代谢、能量代谢,导致靶细胞结构、功能改变,从而引起组织、器官结构功能改变,导致疾病发生。而慢性气道炎症性疾病是以气道阻塞、气道重塑为主要特征的疾病,气道的慢性炎症是其基本特点,越来越多的证据表明微粒与气道慢性炎症性疾病的发生、发展有着密切联系,在气道上皮的损伤与修复过程中起着关键性作用。该综述将阐述微粒在支气管哮喘、COPD 等疾病进程中的作用,以期通过对微粒产生及作用机制的了解,帮助寻找疾病诊疗的新策略。     

Th17与慢性气道炎症性疾病

最近的研究发现了一种新的活化的CD4 T细胞亚群——Th17细胞亚群,它在慢性气道炎症性疾病的发生发展中发挥着重要的作用。Th17细胞亚群分泌产生的细胞因子IL-17可以通过诱导趋化因子CXCL8(IL-8)的释放,促进气道内中性粒细胞募集和激活,与慢性气道炎症性疾病的气道重塑密切相关。另外,Th17细胞亚群是一个与Th1和Th2细胞亚群不同的独立的分支,其分化不依赖于调节传统的Th1和Th2细胞亚群分化的细胞因子和转录因子。鉴于Th17细胞及其细胞因子在气道重塑及慢性气道炎症中的重要作用,本文就Th17与慢性气道炎症性疾病的研究作一综述。     

Th17与慢性气道炎症性疾病

最近的研究发现了一种新的活化的CD4^＋T细胞亚群——Thl7细胞亚群，它在慢性气道炎症性疾病的发生发展中发挥着重要的作用。Thl7细胞亚群分泌产生的细胞因子IL-17可以通过诱导趋化因子CXCL8（IL-8）的释放，促进气道内中性粒细胞募集和激活，与慢性气道炎症性疾病的气道重塑密切相关。另外，Thl7细胞亚群是一个与Thl和Th2细胞亚群不同的独立的分支，其分化不依赖于调节传统的Thl和Th2细胞亚群分化的细胞因子和转录因子。鉴于Thl7细胞及其细胞因子在气道重塑及慢性气道炎症中的重要作用，本文就Thl7与慢性气道炎症性疾病的研究作一综述：     

Toll样受体4与气道慢性炎症性疾病

气道慢性炎症性疾病如慢性阻塞性肺疾病、支气管哮喘等是在各种内外界刺激因素作用下由气道固有细胞、炎症细胞和炎症因子参与的非特异性炎症性疾病.迄今已发现11种Toll样受体(TLR),均为I型跨膜受体蛋白,广泛表达于支气管上皮细胞、支气管平滑肌细胞、树突状细胞、肺泡巨噬细胞等,因其能感知病原体并直接或间接作出防御反应而在慢性气道炎症性疾病的发生发展中发挥重要作用,其中又以TLR4的作用最为突出而成为研究的热点.故深入认识TLR4与慢性气道炎症性疾病的关系将为临床治疗开辟广阔的前景.     

The role of airway smooth muscle in the pathogenesis of airway wall remodeling in chronic obstructive pulmonary disease

Airway wall remodeling processes are present in the small airways of patients with chronic obstructive pulmonary disease, consisting of tissue repair and epithelial metaplasia that contribute to airway wall thickening and airflow obstruction. With increasing disease severity, there is also increased mucous metaplasia and submucosal gland hypertrophy, peribronchial fibrosis, and an increase in airway smooth muscle mass. Apart from its contractile properties, airway smooth muscle produces inflammatory cytokines, proteases, and growth factors, which may contribute to the remodeling process and induce phenotypic changes of the muscle. Airflow limitation responds minimally to beta-agonists and corticosteroid therapy, unlike asthma, perhaps because of alterations in beta-receptor or glucocorticoid receptor numbers, alterations in receptor signaling, or the constrictive limitation imposed by peribronchial fibrosis. Better response is observed with the combination of inhaled long-acting beta-agonists and corticosteroids. This could result from effects at the level of airway smooth muscle. Airway wall remodeling may involve the release of growth factors from inflammatory or resident cells. The influence of smoking cessation or of current therapies on airway wall remodeling is unknown. Specific therapies for airway wall remodeling may be necessary, together with noninvasive methods of imaging small airway wall remodeling to assess responses.     

炎性因子在慢性阻塞性肺疾病气道炎症中的作用

COPD是一种以气道慢性炎症为特征之一的慢性呼吸系统疾病,气道炎性反应在COPD占有重要作用。炎性细胞因子是机体内最重要的一类细胞因子,多种炎性细胞因子参与气道炎症的病理生理机制,对肺组织和支气管产生损害,并发肺外效应。在COPD的自然病程中存在炎性细胞因子网络系统,调控COPD的气道炎症的发生发展。     

The role of biofilms in airway disease

Biofilms are defined as collections of microorganisms attached to a surface and embedded in a matrix. This attached state is the primary mode of microbial growth in the environment and within the body. However, biofilms represent a significant clinical concern because they are recalcitrant to antimicrobial agents. This is particularly troublesome in the respiratory tract where biofilms clearly complicate traditional therapies. This review focuses on the biology, development, and antimicrobial resistance properties of biofilms formed by three significant respiratory tract pathogens; Pseudomonas aeruginosa, Staphylococcus aureus, and Haemophilus influenzae. Recent research has begun to shed light on the molecular events governing biofilm formation and antimicrobial resistance mechanisms with these organisms. A deeper understanding of these concepts will be necessary for the development of rational strategies to control biofilms in the future.     

The role of bacteria in airway inflammation in exacerbations of chronic obstructive pulmonary disease

PURPOSE OF REVIEW: Bacteria cause approximately half of all chronic obstructive pulmonary disease exacerbations. The purpose of this review is to evaluate the status of research on the role of bacteria in airway inflammation during exacerbations and the mechanisms by which bacterial antigens induce inflammation. RECENT FINDINGS: Bacteria in the airways of adults with chronic obstructive pulmonary disease release antigens including endotoxin, peptidoglycan fragments, lipoproteins, and other molecules into the airways. These bacterial antigens induce potent inflammatory effects in the airways. Bacterial exacerbations are associated with systemic inflammation. Studies of Haemophilus influenzae, the most common bacterial cause of exacerbations, reveal that strains associated with exacerbations induce more inflammation compared to colonizing strains. H. influenzae antigens induce production of interleukin-8 and tumor necrosis factor-alpha, activate Toll-like 2 receptors, activate NFkappaB and p38 mitogen-activated protein signaling pathways, and have other inflammatory effects. SUMMARY: Research on the role of bacteria in causing inflammation in chronic obstructive pulmonary disease has been neglected for decades. Research should be directed at further evaluating the role of bacterial antigens in airway inflammation. Reducing or modulating bacterial infection of the airways in chronic obstructive pulmonary disease has the potential to reduce airway inflammation by eliminating an important inciting cause.     

The role of allergy and nonspecific airway hyperresponsiveness in the pathogenesis of chronic obstructive pulmonary disease

Although the information that has been reviewed leaves many questions unanswered, some conclusions can be drawn from available data. (1) Smoking appears to increase the risk of sensitization to certain inhaled antigens encountered in the workplace; however, there is no definite evidence that smoking increases the frequency or intensity of allergy to common aeroallergens in the general population. On average, smokers have higher serum total IgE concentrations and blood eosinophil counts than do nonsmokers, but the mechanisms underlying these alterations are not clear. Analysis of these relationships is complicated by observations suggesting that atopic persons are less likely to become and to remain regular cigarette smokers. (2) Long-term cigarette smoking may be associated with increased nonspecific airway responsiveness, although the magnitude of this effect is relatively small when one adjusts for prechallenge level of pulmonary function. This effect of smoking may be more pronounced in atopic persons. (3) Atopy, as assessed by skin testing and serum IgE concentrations, is associated with asthma, nonspecific airway hyperresponsiveness, and reduced pulmonary function level in population data. However, there is no clear evidence that atopy is a risk factor for irreversible airflow obstruction in persons without asthma. Population data do not indicate how much of the reduction in pulmonary function associated with atopy and asthma is potentially reversible. (4) Blood eosinophil count appears inversely related to the level of pulmonary function and directly related to the rate of decline of pulmonary function among nonsmokers. Reports vary concerning whether the relationship of eosinophil count to level of pulmonary function remains after excluding subjects with diagnosed asthma. This relationship may be determined largely by a clinically distinguishable subset of nonsmokers with "asthmatic bronchitis." Presumably, these observations reflect an adverse impact of eosinophilic inflammation in the airways or lung parenchyma. It is not clear whether this represents an allergic response because skin-test reactivity to common aeroallergens and serum total IgE concentration do not show similar relationships to reduced level and rapid decline of pulmonary function. (5) Among smokers, nonspecific airway hyperresponsiveness appears to be associated with an accelerated longitudinal decline of pulmonary function, although most studies indicating this association are limited by either a retrospective design or lack of adjustment for prechallenge level of pulmonary function.(ABSTRACT TRUNCATED AT 400 WORDS)     

Elafin在气道炎症性疾病中的作用

Elafin是一种内源性的低分子量丝氨酸蛋白酶抑制剂,它来自于其前体trappin-2（或称pre-Elafin）的蛋白水解.Elafin的N端区段可以在转谷酰胺酶的介导下与细胞外基质铰连,而C端可以继续发挥抗蛋白酶作用.此外,Elafin还有抗感染、抗炎和免疫调节作用.因此,在气道炎症性疾病的治疗方面,Elafin是一种极具吸引力的候选分子.     

Defining a role for fibroblasts in the persistence of chronic inflammatory joint disease

The most surprising feature of the inflammatory response in rheumatoid arthritis is not that it occurs but that it does not resolve. The persistence of the chronic inflammatory response in conjunction with ongoing joint destruction is an all too familiar finding in many patients with rheumatoid arthritis. Despite the use of effective anti-inflammatory agents and disease modifying drugs, a significant proportion of patients with rheumatoid arthritis continue to have resistant disease. Complete clinical remission is unusual for more than six months and a formal cure of the disease remains elusive. In this report we focus on how attempts to address the question of why rheumatoid arthritis persists have led to a different interpretation of the pathogenesis of rheumatoid disease; one in which alterations in stromal cells such as fibroblasts play an important role in the switch from resolving to persistent disease.     

The role of beta-catenin in the repair of the damaged airway epithelium in smoking mice]

OBJECTIVE: To evaluate the role of beta-catenin(beta-cat) in the repair of the damaged airway epithelium by comparing their expressions of beta-cat in different stages of smoking in murine model. METHODS: With HE staining, morphological changes of airway epithelium were observed microscopically in mice model at 5th week (S5 w), 10th week (S10 w) and 15th week (S15 w) of smoking. Immunohistochemistry and hybridization in situ were performed to investigate the expressions of beta-cat mRNA, beta-cat, c-Src gene and phospho-rytyrosine-protein (p-Tyr). RESULTS: Morphological changes of the airway epithelium showed predominant damage(S5 w), repair(S10 w) and excessive proliferation (S15 w) Mean beta-cat OD values at S5 w, S10 w and S15 w were 0.097 +/- 0.007, 0.160 +/- 0.003 and 0.107 +/- 0.008, being significantly lower than the control value(0.204 +/- 0.012, all P < 0.01); The mean beta-cat mRNA OD value of S5 w, S10 w and S15 w were (0.123 +/- 0.011, 0.173 +/- 0.008 and 0.116 +/- 0.004) were also lower than that in control(0.223 +/- 0.008, all P < 0.01), but the OD value of S10 w was higher than those of S5 w and S15 w. OD value of S15 w was the lowest with only traced beta-cat mRNA expression in the nuclei. The expressions of c-Src and p-Tyr in normal airway epithelium(OD values: 0.048 +/- 0.015, 0.075 +/- 0.011) were significantly lower than those in S5 w(0.127 +/- 0.018, 0.112 +/- 0.012), S10 w (0.147 +/- 0.010, 0.127 +/- 0.018) and S15 w(0.147 +/- 0.010, 0.127 +/- 0.018, all P < 0.001). CONCLUSION: beta-cat may play an important role in the process of repair of airway epithelium. Downregulation of beta-cat may be caused by c-Src which phosphorylates tyrosin residues of beta-cat, leading to its degradation; Intracellular level of p-Tyr may, to some extent, reflect the functional condition of beta-cat.     

The role of endoscopy in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a group of chronic immune‐mediated disorders of the gastrointestinal tract. It is often the result of the interaction of genetic and environmental factors. The role of endoscopy in disease surveillance is unprecedented. However, there is considerable debate in therapeutic goals in IBD patients, ranging from the resolution of clinical symptoms to mucosal healing. Furthermore, deep remission has recently been advocated for altering disease course in these patients. Additionally, neoplasia continues to be a significant cause of morbidity and mortality in IBD patients. This review discussed the role of several endoscopic techniques in assessing mucosal healing and neoplasia with emphasis on novel non‐invasive endoscopic techniques.