Background-ST2 is an interleukin (IL)-1 receptor family member with membrane-bound (ST2L) and soluble (sST2) isoforms, and sST2 is a biomarker for poor outcome in patients with myocardial infarction (MI). IL-33, the recently discovered ligand for ST2, activates nuclear factor B and thus may regulate apoptotic cell death. We tested the hypothesis that IL-33 is cardioprotective after MI through ST2 signaling. Methods and Results-IL-33 protected cultured cardiomyocytes from hypoxia-induced apoptosis, and this cardioprotection was partially inhibited by sST2. IL-33 induced expression of the antiapoptotic factors XIAP, cIAP1, and survivin. To define the cardioprotective role of IL-33 in vivo, we performed a blinded and randomized study of ischemia/reperfusion in rats. IL-33 reduced cardiomyocyte apoptosis, suppressed caspase-3 activity, and increased expression of IAP family member proteins. IL-33 decreased both infarct and fibrosis volumes at 15 days; furthermore, both echocardiographic and hemodynamic studies revealed that IL-33 improved ventricular function. To determine whether cardioprotection by IL-33 is mediated through ST2 signaling, a randomized and blinded study of ST2

Sumitomo Chemical has developed a low energy consuming and green process for the catalytic oxidation of HCl to Cl 2 , especially when compared with the electrolysis process. The RuO 2 /rutile-TiO 2 catalyst has high catalytic activity and thermal stability due to ultra-fine RuO 2 crystallites that cover the surface of the TiO 2 primary particles with strong interaction. In addition, the silica modified RuO 2 /rutile-TiO 2 catalyst shows higher thermal stability by preventing the RuO 2 sintering due to using dispersed SiO 2 particles. With these catalysts, high reaction rates required for industrial applications are achieved, even at low temperatures.

No abstract

No abstract

A characteristic feature of tissue resident human mast cells (MCs) is their hTryptase-␤-rich cytoplasmic granules. Mouse MC protease-6 (mMCP-6) is the ortholog of hTryptase-␤, and we have shown that this tetramer-forming tryptase has beneficial roles in innate immunity but adverse roles in inflammatory disorders like experimental arthritis. Because the key tissue factors that control tryptase expression in MCs have not been identified, we investigated the mechanisms by which fibroblasts mediate the expression and granule accumulation of mMCP-6. Immature mouse bone marrow-derived MCs (mBMMCs) cocultured with fibroblast-like synoviocytes (FLS) or mouse 3T3 fibroblasts markedly increased their levels of mMCP-6. This effect was caused by an undefined soluble factor whose levels could be increased by exposing FLS to tumor necrosis factor-␣ or interleukin (IL)-1␤. Gene expression profiling of mBMMCs and FLS for receptor⅐ligand pairs of potential relevance raised the possibility that IL-33 was a sought after fibroblast-derived factor that promotes tryptase expression and granule maturation via its receptor IL1RL1/ST2. MCs lacking IL1RL1 exhibited defective fibroblast-driven tryptase accumulation, whereas recombinant IL-33 induced mMCP-6 mRNA and protein accumulation in wild-type mBMMCs. In agreement with these data, synovial MCs from IL1RL1-null mice exhibited a marked reduction in mMCP-6 expression. IL-33 is the first factor shown to modulate tryptase expression in MCs at the mRNA and protein levels. We therefore have identified a novel pathway by which mesenchymal cells exposed to inflammatory cytokines modulate the phenotype of local MCs to shape their immune responses. Mast cells (MCs)2 are granulated cells of the myeloid lineage that reside within connective tissues (1). Although it has been known for some time that MCs complete their differentiation and granule maturation after they exit the bone marrow (2-4), the factors and mechanisms governing the final stages of their development remain poorly understood at the molecular level. Although it was originally proposed that the phenotype of a mature MC was irreversibly determined before its progenitor exits the bone marrow, it is now known that human and mouse MCs exhibit substantial plasticity in their development and that MCs can quickly alter the expression of their granule mediators in a cytokine-dependent manner (2, 5-9).All human MCs contain abundant amounts of hTryptase-␤ (10 -12), which is a tetramer-forming serine protease with tryptic-like substrate specificity (13). The ortholog of hTryptase-␤ is mouse MC protease (mMCP)-6 (14, 15). No human has been identified who lacks MCs, in part, because their tryptase-serglycin proteoglycan complexes are essential for combating bacterial and helminthic infections efficiently (16 -18).In the context of inflammatory arthritis, the number of MCs often increases Ͼ10-fold in the chronically inflamed joint (19). Their prominent roles in experimental arthritis and other MCdependent inflammatory disorders have heightened i...

Background:Chronic stress-induced depressive-like behavior is relevant to inflammatory immune activation. However, the neurobiological alterations in the brain following the central inflammatory immune activation remain elusive.Methods:Therefore, we investigated the neurobiological alterations during depressive-like behavior induced in mice by systemic administration of lipopolysaccharide (LPS; 1.2mg/kg administered twice at a 30-min interval via intraperitoneal injection).Results:At 24h after the second administration of LPS, an increased immobility time in the tail suspension test and the forced swimming test were observed, as well as reduced sucrose preference. Protein levels of the AMPA receptor GluR1 were significantly decreased at the plasma membrane in the medial prefrontal cortex (mPFC) and ventral tegmental area (VTA), while levels of the GluR2 were increased at the plasma membrane in the nucleus accumbens (NAc) at 24h after LPS. However, total GluR1 and GluR2 protein levels in the mPFC, VTA, and NAc were not affected by LPS. Moreover, LPS facilitated release of noradrenaline in the mPFC and VTA, but not in the NAc. Consistently, systemic administration of prazosin, an α1-adrenoceptor antagonist, blocked the LPS-induced downregulation of the membrane GluR1 subunit in both the mPFC and VTA and also blocked the upregulation of the membrane GluR2 subunit in the NAc. Intracerebroventricular administration of prazosin 30min before LPS injection abrogated the LPS-induced depressive-like behaviors. In opposition, administration of propranolol, a β-adrenoceptor antagonist, did not affect the LPS-induced downregulation of GluR1, the upregulation of GluR2, or the depressive-like behavior.Conclusions:These results suggest that LPS-activated α1-adrenoceptor-induced downregulation of membrane GluR1 in the mPFC and VTA is associated with inflammation-induced depressive-like behavior.

No abstract

These results suggest that IL-6-dependent LC neuronal activation induced depression-like behavior and IL-1β-induced increase in leptin levels enhanced α1-adrenoceptor-mediated depression-like behavior.