Fw: Early cell signaling by the cytotoxic enterotoxin of Aeromonas hydrophila in macrophages

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From: " Kathi " <pureheart@...>

Sent: Monday, September 23, 2002 11:52 PM

Subject: Early cell signaling by the cytotoxic enterotoxin of Aeromonas

hydrophila in macrophages

> Thanks to for sending us the following. . .Myrl

>

> ----

>

> Early cell signaling by the cytotoxic enterotoxin of Aeromonas

> hydrophila in

> macrophages

> D. A. Ribardoa, K. R. Kuhla, I. Boldogha, J. W. a, C. W.

> Houstona

> and A. K. Chopraa, f1

>

> a Department of Microbiology and Immunology, University of Texas Medical

>

> Branch, Galveston, TX 77555-1070, U.S.A.

>

> Received 5 October 2001; accepted 2 January 2002. Available online 22

> June

> 2002.

>

> Abstract

> A cytotoxic enterotoxin (Act) of Aeromonas hydrophila is an important

> virulence factor with hemolytic, cytotoxic and enterotoxic activities.

> In

> this report, we demonstrated Act rapidly mobilized calcium from

> intracellular stores and evoked influx of calcium from the extracellular

>

> milieu in macrophages. A direct role of calcium in Act-induced

> prostaglandin

> (e.g. PGE2) and tumor necrosis factor alpha (TNF ) production was

> demonstrated in macrophages using a cell-permeable calcium chelator

> BAPTA-AM, which also down-regulated activation of transcription factor

> NF-B.

> We showed that Act's capacity to increase PGE2 and TNF production could

> be

> blocked by inhibitors of tyrosine kinases and protein kinase A. In

> addition,

> Act caused up-regulation of the DNA repair enzyme redox factor-1

> (Ref-1),

> which potentially could promote DNA binding of the transcription factors

>

> allowing modulation of various genes involved in the inflammatory

> response.

> Taken together, a link between Act-induced calcium release, regulation

> of

> downstream kinase cascades and Ref-1, and activation of NF-B leading to

> PGE2

> and TNF production was established. Since Act also caused extensive

> tissue

> damage, we showed that Act increased reactive oxygen species, and the

> antioxidant N-acetyl cysteine, blocked Act-induced PGE2 and TNF

> production,

> as well as NF- B nuclear translocation in macrophages. We have

> demonstrated

> for the first time early cell signaling initiated in eukaryotic cells by

>

> Act, which leads to various biological effects associated with this

> toxin.

>

> Author Keywords: Aeromonas hydrophila, cytotoxic enterotoxin,

> prostaglandin

> E2, tumor necrosis factor alpha, calcium mobilization, transcription

> factor

> NF-B, reactive oxygen species.

>

>

>