Botulinum toxin blocks mast cells and prevents rosacea like inflammation

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

Matrix metalloproteinase 9 (MMP9) level and MMP9 -1562C>T in patients with obstructive sleep apnea: a systematic review and meta-analysis of case-control studies

BackgroundThe peripheral level of matrix metalloproteinase (MMP)-9 and polymorphism of MMP9 -1562C>T in patients with obstructive sleep apnea (OSA) remains controversial. Therefore, the aims of this systemic review and meta-analysis are to assess the MMP9 level in OSA patients and identify the relationship between MMP9 -1562C>T and OSA susceptibility.MethodsThis systematic review was performed following the PRISMA guideline. We searched for studies in major databases, identifying those indexed from inception to July 3, 2019 which related to MMP9 level, MMP9 -1562C>T and OSA. The pooled standardized mean differences (SMDs) and 95% confidence interval (CI) of MMP9 levels were calculated. In addition, the relationship between MMP9 -1562C>T and OSA susceptibility was assessed by three genetic models. The heterogeneity analysis and calculation of the pooled odds ratio (OR) were also performed, followed by quality assessment using the Newcastle-Ottawa Scale (NOS).ResultsIn sum, our review included 15 eligible studies regarding MMP9 level and three regarding MMP9 -1562C>T. The pooled results showed that peripheral level of MMP9 was increased in OSA patients (SMD = 1.37; 95% CI = 1.15–1.59). Furthermore, significant difference of MMP9 level can be found between severe and mild-to-moderate OSA patients (SMD = 28.17; 95% CI = 4.23–52.11) or between moderate-severe and mild OSA (SMD = 36.62; 95% CI = 12.19–61.04). However, no relationship was observed between MMP9 -1562C>T and OSA susceptibility in three genetic models (Homozygote model, OR = 1.37; 95% CI = 0.87–2.18); (Recessive model, OR = 1.42; 95% CI = 0.83–2.42); (Allele model, OR = 1.07; 95% CI = 0.96–1.18).ConclusionsThis systemic review and meta-analysis indicated that the level of MMP9 was increased in patients with OSA and this increase is relevant to OSA severity. Moreover, the relationship between MMP9 -1562 C>T and OSA susceptibility has currently not been proven by current merging values. Further analyses with larger sample size are required to verify these associations.     

大鼠MMP-13重组腺病毒载体的构建

目的　构建大鼠MMP1 3重组腺病毒载体。方法　将MMP1 3cDNA目的片段插入腺病毒柯氏质粒中 ,再将此质粒与腺病毒DNA末端蛋白复合物共转染 2 93细胞 ,通过同源重组构建MMP1 3 重组腺病毒载体。结果　MMP1 3 重组腺病毒载体经PCR鉴定正确 ,包装纯化后 ,检测病毒滴度为 4× 1 0 9PFU/ml。结论　成功地构建了RatMMP1 3 重组腺病毒载体 ,为下一步行MMP 1 3转基因治疗低顺应性膀胱的研究提供了条件     

Lung Transplant Metalloproteinase Levels Are Elevated Prior to Bronchiolitis Obliterans Syndrome

Parenchymal disease in the allograft lung is associated with interstitial remodeling believed to be mediated by matrix metalloproteinases (MMPs). Recent studies suggest high levels of MMP-9 are associated with bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. Since BOS occurs late in the posttransplant period and may be preceded by episodes of acute rejection or infection, which are associated with interstitial remodeling, we examined MMP profiles in allograft bronchoalveolar lavage (BAL) fluid in the early posttransplant period (preceding BOS). Gelatin zymography, protein array analysis and specific ELISA on BAL fluids from transplanted lungs indicated that MMP-8, MMP-9 and TIMP-1 were strongly expressed in allograft BAL fluid from stable patients, or those with infection or rejection compared to BAL fluid from normal volunteers. Elevated expression of MMP-8, MMP-9 and TIMP-1 occurred early, and was sustained for the 3.2 years covered in this study. Elevations of MMP-8, MMP-9 and TIMP-1 in the first 2 years posttransplant appear to be associated with lung transplantation itself, and not infection or rejection. These data suggest that ongoing and clinically silent MMP activity could perpetuate progressive disease in the allograft lung.     

Matrix Metalloproteinase-2 and Tissue Inhibitor of Metalloproteinase-1 in the Retinal Pigment Epithelium and Interphotoreceptor Matrix: Vectorial Secretion and Regulation

Matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) play an essential role in both normal and pathological extracellular matrix degradation, and a TIMP has been associated with at least one type of retinal degeneration. We have studied expression of MMP-2 and TIMP-1 by zymography, immunocytochemistry, and immunoblotting in the retinal pigment epithelium (RPE) from normal, aged and diseased retinas. MMPs and TIMPs were found in the rat RPE, interphotoreceptor matrix (IPM), and in media conditioned by human and rat RPE in culture. In other polarized cells, MMPs and TIMP-2 are secreted vectorially towards the basal lamina. In the RPE, however, MMP-2 and TIMP-1 were secreted preferentially from the apical surface, the surface bordering the IPM. These findings provide new evidence that MMPs and TIMPs could play a role in the turnover of IPM components.Cell homogenates and conditioned media from RPE isolated from mutant Royal College of Surgeons (RCS) rats with inherited retinal dystrophy had similar amounts of MMP-2 and TIMP-1 as those from congenic control rats. The secretion of MMP-2 and TIMP-1 from RPE cell cultures isolated from young and aged human donors varied widely. However, with increasing cell passage number, secretion of MMPs and TIMPs from human RPE increased dramatically. Also, growing human RPE on bovine corneal endothelial cell-generated extracellular matrix instead of plastic reduced the secretion of both MMPs and TIMPs. These data suggest that the integrity of Bruch's membrane may serve to regulate RPE functions in MMP and TIMP secretion and that extracellular matrices contain signals that regulate MMP and TIMP synthesis and/or secretion by the RPE.     

雷公藤多甙对白细胞介素-1β诱导大鼠滑膜细胞株RSC-364基质金属蛋白酶-3、c-Jun基因表达的影响

目的 观察雷公藤多甙对白细胞介素(IL)-1β诱导大鼠滑膜细胞株RSC-364基质金属蛋白酶-3(MMP3)、c-Jun mRNA表达的影响.方法 选择不同浓度的雷公藤多甙作用IL-1β刺激的大鼠滑膜细胞株RSC-364,37℃,5%CO2的环境下培养48 h,运用酶联免疫吸附试验(ELISA)检测细胞上清的MMP3和实时聚合酶链反应(real-time PCR)检测分析细胞中的c-Jun mRNA表达.结果 不同浓度的雷公藤多甙(0、5、10、20 mg/L)对IL-1β刺激的大鼠滑膜细胞株RSC-364分泌MMP3的水平依次是198、176、140、115 μg/L,c-Jun mRNA表达分别是1.17×106、3.31×105、9.32 ×104、2.81 ×104copies/ml,即呈现明显地抑制.重要的是:c-Jun mRNA表达抑制呈现明显的剂量依赖性.结论 雷公藤多甙治疗类风湿性关节炎的有效的作用机制,可能与其抑制MMP3、c-Jun基因的表达相关.     

Growth factor-dependent activation of the MAPK pathway in human pancreatic cancer: MEK/ERK and p38 MAP kinase interaction in uPA synthesis

Increased expression of the hepatocyte growth factor (HGF) receptor (c-met) and urokinase type plasminogen (uPA) correlated with the development and metastasis of cancers. To investigate the role of HGF/c-met signaling on metastasis in cancer cells stimulated with HGF, we examined the effects of a specific MEK1 inhibitor (PD98059) and a p38 MAP kinase inhibitor (SB203580) on HGF-induced uPA expression in pancreatic cancer cell lines, L3.6PL and IMIM-PC2. Pretreatment of PD98059 decreased HGF-mediated phosphorylation of extracellular receptor kinase (ERK), uPA secretion and expression of matrix metalloproteinases (MMP-2 and MMP-9) in a dose-dependent manner. In contrast, SB203580 pretreatment increased HGF-stimulated ERK phosphorylation, uPA secretion and expression of MMPs. SB203580 also reversed the inhibition of HGF-mediated ERK activation and uPA secretion in the PD98059-pretreated cells. These results suggest that ERK activation by HGF might play important roles in the metastasis of pancreatic cancer and the p38 MAPK pathway also involved in the HGF-mediated uPA secretion and metastasis by regulation of ERK pathway. This revised version was published online in July 2006 with corrections to the Cover Date.