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Airway epithelium is a key component for airway integrity. Previously, we found that expression of the Sec14l3 gene that encodes a 45-kDa secretory protein is inversely associated with the progression of experimentally induced airway inflammation and degeneration/necrosis of alveolar epithelium. In this report, using in situ hybridization we demonstrated that the ciliated cells in mouse lung selectively express Sec14l3 mRNA. In a three-dimensional culture of mouse tracheal epithelial cells, levels of the Sec14l3 mRNA correlated with the differentiation of ciliated cells. Intranasal infection of adult mice with influenza virus resulted in a 20-fold, progressive decrease in Sec14l3 mRNA expression over 10 days post infection. These results enhance the potential value of Sec14l3 as a ciliated epithelial cell-specific biomarker for the progression of airway inflammations such as airway viral infection and asthma. [ABSTRACT FROM AUTHOR]

Obesity is a life-threatening factor and is often associated with dysregulation of gene expression. Here, we show that the CNOT3 subunit of the CCR4-NOT deadenylase complex is critical to metabolic regulation. Cnot3+/? mice are lean with hepatic and adipose tissues containing reduced levels of lipids, and show increased metabolic rates and enhanced glucose tolerance. Cnot3+/? mice remain lean and sensitive to insulin even on a high-fat diet. Furthermore, introduction of Cnot3 haplodeficiency in ob/ob mice ameliorated the obese phenotype. Hepatic expression of most mRNAs is not altered in Cnot3+/? vis-à-vis wild-type mice. However, the levels of specific mRNAs, such as those coding for energy metabolism-related PDK4 and IGFBP1, are increased in Cnot3+/? hepatocytes, having poly(A) tails that are longer than those seen in control cells. We provide evidence that CNOT3 is involved in recruitment of the CCR4-NOT deadenylase to the 3? end of specific mRNAs. Finally, as CNOT3 levels in the liver and white adipose tissues decrease upon fasting, we propose that CNOT3 responds to feeding conditions to regulate deadenylation-specific mRNAs and energy metabolism. [ABSTRACT FROM AUTHOR]

In this study, we aimed to assess the role of helper T cells in the development of gastric lymphoid follicles induced by Helicobacter suis infection. C57BL/6J mice were orally inoculated with H. suis. Six weeks after infection, gastric lymphoid follicles were observed in the gastric mucosa by hematoxylin and eosin staining, and the number of follicles was increased throughout the infection period. An immunohistological examination showed that the lymphoid follicles were composed of B cells, CD4-positive helper T cells, and dendritic cells (DC). It was also revealed that the mRNA expression level of interferon-γ (IFN-γ) in the gastric mucosa was significantly increased at 12 weeks after infection. No gastric lymphoid follicles were detected in IFN-γ-deficient mice that had been infected with H. suis at 12 weeks after infection, although the development of lymphoid follicles in IL-4-deficient mice infected with H. suis was similar to that seen in the wild-type mice. In conclusion, IFN-γ, a Th1 cytokine, is deeply involved in the pathogenesis of gastric lymphoid follicles induced by H. suis infection, and it is suggested that CD4-positive T cells and DC aid in the expansion of gastric lymphoid follicles. [ABSTRACT FROM AUTHOR]

Abstract: The present study was designed to investigate the possible involvement of TLR4 pathway in the mouse hippocampus following toluene exposure. Male C3H/HeN and C3H/HeJ (TLR4 defective) mice were exposed to 0, 5, 50 or 500ppm of toluene for 6weeks. The expressions of TLR4-related signal transduction pathway mRNAs in the hippocampi were examined using real-time RT-PCR and an immunohistochemical analysis. In C3H/HeN mice, the relative mRNA expression levels of TLR4 and NF-κB activating protein were significantly up-regulated in the groups exposed to toluene, but not in the C3H/HeJ mice. Heat shock protein 70, a possible endogenous ligand for TLR4, mRNA was increased in the C3H/HeN mice exposed to toluene. This is the first report to show that TLR4 may have a role in the neurotoxic effects in mice exposed to toluene. [Copyright &y& Elsevier]

Abstract: We previously reported that a population of allograft (H-2DdKd)-induced macrophages (AIM) in C57BL/6 (H-2DbKb) mice exhibited major histocompatibility complex (MHC) haplotype (H-2Dd or H-2Kd)-specific killing of allografts in a macrophage MHC receptor 1 or 2 (MMR1 or 2)-dependent manner. In the present study, we isolated a cDNA encoding a human homologue (83.6% amino-acid identity) of mouse MMR2 from a human cDNA library, the donors of which had never been allografted. The cDNA (2376-bp) encoded a 791-amino-acid polypeptide with a calculated molecular mass of 91kDa. Unexpectedly, the mRNA was expressed at least in part in peripheral blood mononuclear cells (PBMCs) or monocytes, but not in granulocytes or lymphocytes. The expression varied from volunteer to volunteer: PBMCs from 8 volunteers expressed human MMR2 at similar levels, whereas those from 8 other volunteers showed no or much less expression of it. Flow cytometric analyses revealed that HEK293T cells expressing human MMR2 protein bound fluorescein-labeled HLA-B62, but not A2, A-11, A-24 or B7, with a dissociation constant (=8.9×10−9 M) and that the interaction was completely inhibited by the addition of R12 mAb specific for mouse MMR2. Similarly, the expression of mouse MMR2 varied from strain to strain in mice: PBMCs from 9 non-H-2Kd, but not from 3 H-2Kd, mice expressed mouse MMR2 specific for H-2Kd. These results suggest that human MMR2 on monocytes may be a novel receptor for HLA-B62. [Copyright &y& Elsevier]

In mammals, the circadian and stress systems (both centers of which are located in the hypothalamus) are involved in adaptation to predictable and unpredictable environmental stimuli, respectively. Although the interaction and relationship between these two systems are intriguing and have been studied in different ways since the ‘pre-clock gene’ era, the molecular interaction between them remains largely unknown. Here, we show by systematic molecular biological analysis that acute physical stress elevated only Period1 (Per1) mRNA expression in mouse peripheral organs. Although behavioral rhythms in vivo and peripheral molecular clocks are rather stable against acute restraint stress, the results of a series of promoter analyses, including chromatin immunoprecipitation assays, indicate that a glucocorticoid-responsive element in the Perl promoter is indispensable for induction of this mRNA both in vitro and in vivo. These results suggest that Per1 can be a potential stress marker and that a third pathway of Perl transcriptional control may exist in addition to the clock-regulated CLOCK-BMAL1/E-box and light-responsive cAMP-responsive element -binding protein/cAMP-responsive element pathways. [ABSTRACT FROM AUTHOR]