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Anti-Inflammatory Effects of Moxifloxacin on Activated Human Monocytic Cells: Inhibition of NF-  B and Mitogen-Activated Protein Kinase Activation and of Synthesis of Proinflammatory Cytokines.Taly Weiss, 2004.We previously showed that moxifloxacin (MXF) exerts protective anti-inflammatory effects in immunosuppressed mice infected with Candida albicans by inhibiting interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-  ) production in the lung . Immunohistochemistry demonstrated inhibition of nuclear factor (NF)-B translocation in lung epithelium and macrophages in MXF-treated mice . In the present study we investigated the effects of MXF on the production of proinflammatory cytokines (i.e., IL-8, TNF-, and IL-1ß) by activated human peripheral blood monocytes and THP-1 cells and analyzed the effects of the drug on the major signal transduction pathways associated with inflammation: NF-B and the mitogen-activated protein kinases ERK and c-Jun N-terminal kinase (JNK) . The levels of IL-8, TNF-, and IL-1ß secretion rose 20- and 6.7-fold in lipopolysaccharide (LPS)-activated monocytes and THP-1 cells, respectively . MXF (5 to 20 µg/ml) significantly inhibited cytokine production by 14 to 80% and 15 to 73% in monocytes and THP-1 cells, respectively . In THP-1 cells, the level of NF-B nuclear translocation increased fourfold following stimulation with LPS-phorbol myristate acetate (PMA), and this was inhibited (38%) by 10 µg of MXF per ml . We then assayed the degradation of inhibitor (I)-B by Western blotting . LPS-PMA induced degradation of I-B by 73%, while addition of MXF (5 µg/ml) inhibited I-B degradation by 49% . Activation of ERK1/2 and the 46-kDa p-JNK protein was enhanced by LPS and LPS-PMA and was significantly inhibited by MXF (54 and 42%, respectively, with MXF at 10 µg/ml) . We conclude that MXF suppresses the secretion of proinflammatory cytokines in human monocytes and THP-1 cells and that it exerts its anti-inflammatory effects in THP-1 cells by inhibiting NF-B, ERK, and JNK activation . Its anti-inflammatory properties should be further assessed in clinical settings .
Atomic Force Microscopy, a Powerful Tool in Microbiology. Yves F. Dufrêne, 2002. Complete Genome Sequence of the Oral Pathogenic Bacterium Porphyromonas gingivalis Strain W83. Karen E. Nelson, 2003.The complete 2,343,479-bp genome sequence of the gram-negative, pathogenic oral bacterium Porphyromonas gingivalis strain W83, a major contributor to periodontal disease, was determined . Whole-genome comparative analysis with other available complete genome sequences confirms the close relationship between the Cytophaga-Flavobacteria-Bacteroides (CFB) phylum and the green-sulfur bacteria . Within the CFB phyla, the genomes most similar to that of P . gingivalis are those of Bacteroides thetaiotaomicron and B . fragilis . Outside of the CFB phyla the most similar genome to P . gingivalis is that of Chlorobium tepidum, supporting the previous phylogenetic studies that indicated that the Chlorobia and CFB phyla are related, albeit distantly . Genome analysis of strain W83 reveals a range of pathways and virulence determinants that relate to the novel biology of this oral pathogen . Among these determinants are at least six putative hemagglutinin-like genes and 36 previously unidentified peptidases . Genome analysis also reveals that P . gingivalis can metabolize a range of amino acids and generate a number of metabolic end products that are toxic to the human host or human gingival tissue and contribute to the development of periodontal disease .
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