Local production and localization of transforming growth factor-beta in tuberculous pleurisy.

Transforming growth factor-beta (TGF-beta) is one of the cytokines which play an immunosuppressive role in an inflammatory process. To investigate the local production of TGF-beta, we evaluated the levels of TGF-beta in tuberculous pleural effusions (TBPE) and non-tuberculous benign pleural effusions (non-TBPE) by the growth inhibition assay with Mv1Lu mink lung epithelial cells. The mean level of TGF-beta in TBPE (46.1 +/- 31.5 pM; mean +/- s.d.) was higher than in non-TBPE (21.7 +/- 12.3 pM) (P < 0.05). Although the level of interferon-gamma (IFN-gamma) in TBPE measured by ELISA was significantly higher than in non-TBPE, there was no significant difference in the levels of tumour necrosis factor-alpha (TNF-alpha) measured by ELISA between these two groups. Moreover, to elucidate localization of TGF-beta in tuberculous pleurisy, immunohistochemical studies of pleura, using the rabbit polyclonal antibody Ab39 against latent TGF-beta 1 binding protein (LTBP) were performed. Results revealed that LTBP was localized in immature fibrotic areas where infiltrations of T lymphocytes and macrophages were absent. Importantly, the major sources of LTBP in these areas were thought to be mesothelial cells and fibroblasts. LTBP was not found in granulomas and mature fibrotic areas. Our data suggest that TGF-beta in tuberculous pleurisy may play important roles for regression of granulomatous inflammation and pleural fibrosis for tissue repair.     

Effect of ozone exposure on allergic sensitization and airway inflammation induced by dendritic cells

BACKGROUND: Epidemiological studies suggest that ozone exposure is related to increased asthma symptoms. Dendritic cells (DCs) are the principal antigen-presenting cells in the airways. OBJECTIVE: We have examined whether ambient doses of ozone (100 ppb for 2 h) enhance allergic sensitization and/or airway inflammation in a mouse model. METHODS: C57BL/6 mice were sensitized to inhaled ovalbumin (OVA) by intratracheal instillation of OVA-pulsed DCs on day 0. Daily exposure to OVA aerosol on days 14-20 resulted in an eosinophilic airway inflammation, as reflected in bronchoalveolar lavage fluid and lung histology. In a first experiment, mice were exposed to ozone or room air immediately prior to and following sensitization. Subsequently, we tested the effect of ozone exposure during antigen challenge in DC-sensitized mice. RESULTS: Exposure to ozone during sensitization did not influence airway inflammation after subsequent allergen challenge. In contrast, in sensitized mice, challenge with OVA together with ozone (days 14-20) resulted in enhanced airway eosinophilia and lymphocytosis, as compared with mice exposed to OVA and room air (1.91 x 106 +/- 0.46 x 106 vs. 0.16 x 106 +/- 0.06 x 106 eosinophils/mL lavage fluid; P = 0.015; 0.49 x 106 +/- 0.11 x 106 vs. 0.08 x 106 +/- 0.03 x 106 lymphocytes/mL lavage fluid; P = 0.004). Ozone exposure without subsequent OVA exposure did not cause airway inflammation. CONCLUSION: Ozone exposure does not increase allergic sensitization but enhances antigen-induced airway inflammation in mice that are sensitized via the airways.     

The persistence of interleukin-6 is regulated by a blood buffer system derived from dendritic cells

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Airway eosinophilia and expression of interleukin-5 protein in asthma and in exacerbations of chronic bronchitis

Background An increased nutnber of eosinophils in the bronchial mucosa has been demonstrated both in asthma and in exacerbations of chronic bronchitis. Oiyective To investigate whether the airway eosinophilia present in asthma and in chronic bronchitis during exacerbations is associated with interleukin (IL)-5 protein expression in the bronchial mucosa. Methods We obtained bronchial biopsies in 18 subjects with asthma (four intrinsic, seven extrinsic and seven occupational) and in II subjects with chronic bronchitis examined during an exacerbation. The findings were compared wilh those of bronchial biopsies from 10 subjects with chronic bronchitis examined under baseline conditions and from seven normal subjects, taken as controls. By immunohistochemistry, we assessed the expression of IL-5 protein and the number of eosinophils (EG2), mast cells ftryptase), and T-lymphocytes (CD3) in the submucosa. Results As compared with controls, the number of eosinophils was increased to a similar degree in both asthma (P < 0.001) and in exacerbations of ehronic bronchitis (P < 0.001). whereas the number of I L-5 immunopositive cells was increased significantly only in asthma (P < 0.01). No diflerences were observed in the number of tnast cells and T-lymphocytes between the four groups of subjects examined. Conciusions This study shows that the degree of airway eosinophilia is similar in asthma and in exacerbations of ehronic bronchitis, but only in asthma is it associated with an increased expression of I L-5 protein in the bronchial tnucosa.     

Enhancement of NF-kappaB activity by resveratrol in cytokine-exposed mesangial cells

Resveratrol, a natural polyphenolic phytoalexin, has been considered as a potential anti-inflammatory agent because of its suppressive effect on nuclear factor-kappaB (NF-kappaB). However, we recently found that treatment of glomerular mesangial cells with resveratrol significantly and dose-dependently enhanced NF-kappaB activation triggered by proinflammatory cytokines. This finding was evidenced by different reporter assays as well as by expression of an endogenous NF-kappaB-dependent gene, intercellular adhesion molecule-1. The NF-kappaB promoting effect of resveratrol was also observed in renal tubular LLCPK1 cells, but not in HepG2 hepatoma cells. In all cell types tested, treatment with resveratrol alone did not affect NF-kappaB activity. The enhanced activation of NF-kappaB by resveratrol progressed for at least 24 h and was accompanied by sustained down-regulation of an endogenous NF-kappaB inhibitor, IkappaBbeta, but not IkappaBalpha. Although expression of inducible nitric oxide synthase was suppressed by resveratrol, nitric oxide, a negative regulator of NF-kappaB, was not involved in the regulation of NF-kappaB by resveratrol. These data elucidated, for the first time, that resveratrol may enhance activation of NF-kappaB under certain circumstances.     

Engulfment of mast cell secretory granules on skin inflammation boosts dendritic cell migration and priming efficiency

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小胶质细胞极化介导炎症反应在脊髓损伤中的作用

背景:小胶质细胞极化参与脊髓损伤后的炎症反应,并在其中发挥关键作用。相关研究表明,有效诱导小胶质细胞从M1促炎表型向M2抗炎表型极化,可以减轻脊髓损伤后的炎症反应,促进组织的修复再生和神经功能的恢复。目的:文章对小胶质细胞的功能和极化、小胶质细胞极化对脊髓损伤的影响及其潜在调控策略以及脊髓损伤后炎症反应进行综述。方法:检索PubMed、Web of Science和中国知网数据库,英文检索词为“microglia,polarization,spinal cord injury,inflammation”,中文检索词为“小胶质细胞、极化、脊髓损伤、炎症”,按纳入和排除标准共纳入80篇文献进行总结。结果与结论:①由小胶质细胞介导的稳定而持续的炎症反应,对脊髓损伤的预后至关重要。②在生理条件下,小胶质细胞处于M0静止表型,但在脊髓损伤后,小胶质细胞活化,进而极化成M1促炎表型,导致神经组织修复能力降低和出现持续性神经炎症。③在脊髓损伤的炎症反应过程中,调控小胶质细胞向M2表型极化或至少向M2表型倾斜,有利于抑制氧化应激反应、调节突触重塑、促进轴突再生和血管生成,是一种有效的调控策略。④截止到目前的研究表明,间充质干细胞、外泌体、临床药物、天然产物、miRNAs和靶点分子可调控小胶质细胞在M1和M2表型之间的转换,这为脊髓损伤后神经组织的修复提供了一种新的思路,未来需进一步研究小胶质细胞在脊髓损伤过程中调控极化的详细机制。     

Investigation of association of 13 polymorphisms in eight genes in southeastern African American Alzheimer disease patients as compared to age‐matched controls

Alzheimer disease (AD) is an emotionally devastating and exceptionally costly disease. Apolipoprotein E (APOE) is a major risk factor gene for AD regardless of age of onset or family history. However, this association may not be as strong or consistent in ethnic groups such as African Americans, raising the possibility of other modifier gene(s). In a group of African American AD patients, a significantly increased risk of AD was associated with two E4 alleles (OR = 5.6; 95% CI = 1.5–21.0) or one E4 allele (OR = 2.5; 95% CI = 1.3–5.0) when compared to E3/E3 genotype, and there was a significant lowering of age of onset for affecteds with E4/E4 genotype as compared to one E2 allele (P = 0.02) or all others (P = 0.03). We also found a significant increase in age of onset with the ?308 #2 (A) allele of TNF when compared to AD cases with no #2 allele. A significant increase in age was also demonstrated with the #2 allele (99 base pairs) of the microsatellite TNFa, located ～ 10.5 kb upstream of TNF. When these two alleles were combined with the TNF ?238G (#1) allele to give a haplotype, the significant increase in age was still demonstrated. Polymorphisms in the APOE promoter and six other candidate genes did not appear to demonstrate any significant association with our African American AD patients. Our results confirm the established association of APOE4 to AD observed in several ethnic groups, including African Americans. In addition, TNF appears to have some modifying effect in AD, primarily on age of onset, or it could be in linkage disequilibrium with a modifier locus nearby. © 2001 Wiley‐Liss, Inc.