In response to Salmonella typhimurium, the intestinal epithelium generates an intense inflammatory response consisting largely of polymorphonuclear leukocytes (neutrophils, PMN) migrating toward and ultimately across the epithelial monolayer into the intestinal lumen. It has been shown that bacterial-epithelial cell interactions elicit the production of inflammatory regulators that promote transepithelial PMN migration. Although S. typhimurium can enter intestinal epithelial cells, bacterial internalization is not required for the signaling mechanisms that induce PMN movement. Here, we sought to determine which S. typhimurium factors and intestinal epithelial signaling pathways elicit the production of PMN chemoattractants by enterocytes. Our results suggest that S. typhimurium activates a protein kinase C-dependent signal transduction pathway that orchestrates transepithelial PMN movement. We show that the type III effector protein, SipA, is not only necessary but is sufficient to induce this proinflammatory response in epithelial cells. Our results force us to reconsider the long-held view that Salmonella effector proteins must be directly delivered into host cells from bacterial cells.

Recebido em 15/5/02; aceito em 18/11/02 AN OVERVIEW OF THE CHEMISTRY AND PHARMACOLOGY OF NAPHTHOQUINONES WITH EMPHASIS ON β-LAPACHONE AND DERIVATIVES. Naphthoquinones have been extensively studied due to their activity as topoisomerase inhibitors. These enzymes are critical to DNA replication in cells. In addition, naphthoquinones have been shown to induce what are known as "reactive oxygen species" that can cause damage to cells. β-Lapachone is a very important pyranaphthoquinone obtained from the heartwood of the lapacho tree, Tabebuia avellanedae Lorentz ex. Griseb. (Bignoniaceae), and other Tabebuia trees native to Central and South America and chemically from lapachol. β-Lapachone has a diversity of useful biological activities against various cancer cell lines such as human ovarian and prostate tumors and, at lower doses is a radiosensitizer of several human cancer cell lines. It gives rise to a variety of effects in vitro including the inhibition or activation of topoisomerase I an II in a distinct manner from that of other topoisomerase inhibitors. This review intend to discuss some details of the mechanisms of quinone-induced cell damage and death, and we also summarize results of the literature indicating that b-Lapachone may take part in quinone-elicited apoptosis despite the fact that its mechanism of action in vivo and its targets are still unknown.Keywords: beta-Lapachone; naphthoquinone; pyranaphthoquinone; apoptosis. INTRODUÇÃOAs quinonas representam uma ampla e variada família de metabólitos de distribuição natural 1,2 . Nos últimos anos intensificouse o interesse nestas substâncias, não só devido à sua importância nos processos bioquímicos vitais, como também ao destaque cada vez maior que apresentam em variados estudos farmacológicos. Na natureza, estão envolvidas em etapas importantes do ciclo de vida de seres vivos, principalmente nos níveis da cadeia respiratória e da fotossíntese, como por exemplo as ubiquinonas (1a) e as plastoquinonas (1b) 3 . As naftoquinonas, por exemplo as vitaminas do tipo K (2), de irrestrita necessidade aos seres vivos 4 , possuem ação controladora da coagulação sanguínea.De um modo geral, as quinonas naturais mais representativas são de vital importância para vegetais superiores, artrópodes, fungos, liquens, bactérias, algas e vírus. A distribuição dessas substân-cias nos variados organismos implica, possivelmente, em funções biológicas múltiplas, agindo de forma conspícua em seus diversos ciclos bioquímicos.Em estudos farmacológicos as quinonas mostram variadas biodinamicidades, destacando-se, dentre muitas, as propriedades microbicidas, tripanossomicidas, viruscidas, antitumorais e inibidoras de sistemas celulares reparadores, processos nos quais atuam de diferentes formas. Como exemplo, destaca-se o estresse oxidativo que provocam, ao induzirem a formação deletéria endógena de espécies bioativas derivadas do oxigênio ( 1 O 2 , . OH, O 2 .-e H 2 O 2 ) 5 , como ocorre no Trypanosoma cruzi, agente causador da doença de Chagas. Outra atividade marcante destas subst...

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