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Biomedical subjects

Marie-Thérèse Labro

Publications and source records attributed to Marie-Thérèse Labro.

6 recordsLinked to original sources

The macrolide roxithromycin impairs NADPH oxidase activation and alters translocation of its cytosolic components to the neutrophil membrane in vitro.

We have studied the interference of roxithromycin with NADPH oxidase, the key enzymatic system for oxidant production by human neutrophils. Roxithromycin alters the reconstitution of an active enzyme and impairs the translocation to the outer membrane of the cytosolic components p47-phox and p67-phox. Interestingly, in resting cells roxithromycin directly triggers the translocation of these factors without stimulating the oxidative burst.

Anti-Bacterial Agents↗

Modulation of tissue factor expression by rapamycin and FK-506 in lipopolysaccharide-stimulated human mononuclear cells and serum-stimulated aortic smooth muscle cells.

Inflammation is a key pathogenic component of atherosclerosis; it also promotes thrombosis, a process underlying acute coronary events and stroke. Cells present in atherosclerotic plaque show abnormal tissue factor (TF) expression. Macrolides, in addition to their antimicrobial properties, have antiinflammatory effects that might help prevent atherothrombosis. The aim of this study was to determine the effect of an immunosuppressant macrolide, rapamycin (Sirolimus), on the expression of TF and its inhibitor (TFPI) by monocytic cells (human blood mononuclear and THP-1 cells) and human aortic smooth muscle cells, in comparison with FK-506 and azithromycin. In monocytic cells, rapamycin and FK-506 inhibited LPS-induced TF activity, antigen and mRNA expression through a transcriptional mechanism involving NF-kappaB. In smooth muscle cells, rapamycin and azithromycin had no effect on serum-induced TF expression, while FK-506 increased serum-induced TF protein and mRNA expression. TFPI levels in the culture supernatants of serum-stimulated smooth muscle cells were not modified by any of the three macrolides. Rapamycin slightly inhibits TFPI induction by LPS in monocytic cells. In addition to its recently established efficacy in the prevention of stent restenosis, the inhibitory effect of rapamycin on the TF pathway might have interesting therapeutic implications.

Anti-Bacterial Agents↗

Anti-inflammatory activity of ansamycins.

Inflammation represents a complex biologic and biochemical process involving cells of the immune system and a plethora of biologic mediators in response to mechanical, chemical or infectious injuries. When mobilization of effector cells and molecules becomes excessive, the beneficial aspect of this response--to limit damage and promote healing, can be overriden, resulting in host-cell and tissue dysfunction. Based on the hypothesis that chronic infections underly some inflammatory diseases, antibacterial therapy has long been assessed in various inflammatory settings. Recently, the anti-inflammatory activity of some antibacterial agents has also been suspected. Of these duel-action drugs, ansamycins represent an interesting family. Although their therapeutic use is restricted to potentially infectious inflammatory diseases, many experimental data suggest that these drugs also possess direct inhibitory activity on some crucial proinflammatory effectors. To date, the potent antimycobacterial activity of the therapeutically useful ansamycins precludes their widespread use in inflammatory diseases. However, biosynthetic manipulation remains an attractive route for the generation of pharmacologically useful analogs.

Animals↗

Macrolide antibiotics: current and future uses.

After a long history of anti-infective therapeutic use, macrolide antibiotics have not yet given up all their secrets. Interest in their therapeutic potential in inflammatory diseases (possibly including non-infectious diseases) has generated abundant fundamental research and therapeutic trials worldwide. The main question regarding the future prospects of this class of drugs is whether some macrolides are beneficial in such settings because they modulate host inflammatory responses (and cellular targets) or rather because they eliminate a latent, unidentified pathogen which triggers chronic inflammation. However, no clearcut results have yet been obtained.

Anti-Infective Agents↗

Cellular and molecular effects of macrolides on leukocyte function.

Macrolide antimicrobials have stimulated worldwide interest owing to their therapeutic effects in various inflammatory, apparently non infectious, diseases. Abundant data are now available on their interactions with host cell (specially phagocyte) functions. Modulation of oxidant production by neutrophils and of pro-inflammatory cytokine synthesis and release by leukocytes are the two main effects observed in vitro. However, despite an extensive literature, many questions remain, such as the cellular/microbial target(s) of macrolide action, the critical chemical structure(s), and the usefulness of combining antimicrobial and anti-inflammatory properties, which during long-term treatment, could lead to increased microbial resistance. Also, because of the multiplicity of macrolide effects on different cell subsets, a unifying hypothesis for macrolide interactions with host cells is lacking. Novel analytical methods will certainly lead to new macrolide-based therapeutic strategies in cancer and inflammation.

Animals↗