ABSTRACT
LaCrO3 was prepared by using the polymeric precursor method for use as a receptor material and its NOx sensing characteristics were investigated. Nano-LaCrO3 powders were synthesized at the optimum compositions of the mole ratio of [La-, Cr-source]:[EG]:[AcAc] = [a, a]:[160 a]:[8 a] with 1 wt% polyvinylpyrrolidone (PVP) using ethylene glycol (EG) as a solvent, acetyl acetone (AcAc) as a chelating agent, and PVP as a polymer additive. The thermal decomposition behavior, crystal structure, morphology, and particle sizes of nano powders were characterized by a thermal analysis (TG-DTA), X-ray diffraction (XRD), a field emission scanning electron microscopy (FE-SEM), and a particle size analyzer, respectively LaCrO3 powders were mainly orthorhombic in structure and the primary particle size was 30 nm according to the XRD results. All solid-state compact impedancemetric-type sensor devices composed of Li1.5Al0.5Ti1.5(PO4)3 (LATP) as a transducer and a perovskite-type LaCrO3 nano powder as a receptor, have been investigated for their ability to detect NOx (NO and NO2) in the range of 1-250 ppm at 400 degrees C. The sensor device showed high gas sensitivities at NO gas, but relatively low gas sensitivities for NO2 gas.
ABSTRACT
IL-1 is one of the key mediators involved in the pathogenesis of rheumatoid arthritis (RA) and is known to affect the level of gene expression in various settings. We investigated the effects of IL-1beta on the expression of 240 genes in rheumatoid synovial fibroblasts (RSFs) using a cDNA microarray. Total RNAs were prepared from RSFs stimulated with IL-1beta and hybridized to the microarray. The fluorescence intensity of each gene was compared between the control and IL-1beta-treated cells. To confirm the data obtained from the microarray analysis, the level of gene expression was also examined by ELISA, Northern blot, or Western blot depending on the genes to be analyzed. The genes whose levels were significantly changed by IL-1beta in the microarray analysis could be divided into three categories; inflammatory mediators, matrix-modifying enzymes, and apoptosis-associated molecules. The increase in the mRNA levels of IL-6, IL-8, MCP-1, and GRO-1 was confirmed by determining their protein levels from the cell culture supernatant using ELISA. The increase in the level of two matrix-degrading enzymes, MMP-1 and MMP-3, was reproducibly observed by an ELISA method, while the decrease in the level of TIMP-3, an inhibitor of MMPs, was confirmed by Northern blot analysis. The fluorescence intensity of two apoptosis-related genes, caspase-3 and Bcl-xL, was significantly lowered. The decreased protein level of caspase-3 was also found. Our data suggested that IL-1beta could provoke a series of responses in RSFs leading to the pathologic status of RA, including enhancement of inflammatory cytokines, imbalanced production of MMPs and TIMPs, and dysregulation of apoptosis.
Subject(s)
Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/immunology , Fibroblasts/drug effects , Gene Expression Regulation , Interleukin-1/pharmacology , Synovial Membrane/cytology , Animals , Apoptosis/physiology , Arthritis, Rheumatoid/pathology , Cells, Cultured , Chemokine CCL2/genetics , Chemokine CCL2/metabolism , Chemokine CXCL1 , Chemokines, CXC/genetics , Chemokines, CXC/metabolism , Fibroblasts/cytology , Fibroblasts/physiology , Gene Expression Profiling , Humans , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Interleukin-1/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Interleukin-8/genetics , Interleukin-8/metabolism , Male , Matrix Metalloproteinases/genetics , Matrix Metalloproteinases/metabolism , Oligonucleotide Array Sequence Analysis , RNA/metabolismABSTRACT
OBJECTIVE: To determine the efficacy of local therapy with human angiostatin gene in murine collagen-induced arthritis (CIA). METHODS: DBA/1 mice were immunized with bovine type II collagen. Before the onset of arthritis, NIH3T3 fibroblasts, transduced with angiostatin-expressing retroviral vectors or control vectors, were transplanted into the knee cavity. The incidence of arthritis in the knee joints was evaluated histologically based on pannus formation and cartilage destruction. Paws were evaluated macroscopically for redness, swelling, and deformities and immunologically for levels of interleukin-1 beta. Angiogenesis in paws and knee joints was studied by immunohistochemistry using anti-CD31 antibody and measurement of von Willebrand factor levels. RESULTS: Pannus formation and cartilage erosion were dramatically reduced in knees transplanted with angiostatin-expressing cells. In addition, the onset of CIA in the ipsilateral paws below the knees injected with the angiostatin gene was significantly prevented. Furthermore, angiostatin gene transfer inhibited arthritis-associated angiogenesis. CONCLUSION: Local production of angiostatin in the knee was able to prevent the onset of CIA not only in the knee injected with genetically engineered cells, but also in the uninjected ipsilateral paw. This suggests that transfer of the angiostatin gene, and potentially also its protein, may provide a new, effective approach to the treatment of rheumatoid arthritis.
