Message Number: FHL13067 | New FHL Archives Search
From: Sukie Crandall
Date: 2011-03-27 15:42:45 UTC
Subject: [ferrethealth] abstract
To: fhl <>

> Chest. 2011 Mar 24. [Epub ahead of print]
> Dapsone inhibits IL-8 secretion from human bronchial epithelial cells sti=
mulated with LPS and resolves airway inflammation in the ferret.
> Kanoh S, Tanabe T, Rubin BK.
> Pediatrics, Virginia Commonwealth University School of Medicine, Richmond=
> Abstract
> Abstract
> BACKGROUND: IL-8 is an important activator and chemoattractant for neutro=
phils that is produced by normal human bronchial epithelial (NHBE) cells th=
rough mitogen-activated protein kinase (MAPK) and nuclear factor-=CE=BAB (N=
F-=CE=BAB) p65 pathways. Dapsone, a synthetic sulfone, is widely used to tr=
eat chronic neutrophil dermatoses. We investigated the effects of dapsone o=
n polarized IL-8 secretion from LPS-stimulated NHBE cells, and further eval=
uated its ability to decrease LPS-induced inflammation in the ferret airway=
> METHODS: NHBE cells were grown at air-liquid interface (ALI) to ciliated =
differentiation. Baseline and endotoxin (LPS) stimulated-IL-8 secretion was=
measured by ELISA at air and basal sides with and without dapsone. Western=
blotting was used to determine signaling pathways. In vivo, ferrets were e=
xposed to intratracheal LPS over a period of five days. Once inflammation w=
as established, oral or nebulized dapsone was administered for 5 days. Intr=
aepithelial neutrophil accumulation was analyzed histologically and mucocil=
iary transport was measured on the excised trachea.
> RESULTS: Dapsone 1=CE=BCg/ml did not influence unstimulated (basal) IL-8 =
secretion. Apical LPS stimulation induced both apical and basolateral IL-8,=
but basolateral LPS increased only basolateral IL-8. Dapsone inhibited pol=
arized IL-8 secretion from ALI-conditioned cells. Dapsone also decreased LP=
S-induced IL-8 mRNA level. LPS led to phosphorylation of extracellular sign=
al regulated kinase (ERK)1/2, but not p38 MAPK or c-Jun N-terminal kinase. =
LPS also induced NF-=CE=BAB p65 phosphorylation, an effect that was inhibit=
ed by dapsone. Both oral and aerosol dapsone decreased LPS-induced intraepi=
thelial neutrophil accumulation but only treatment with aerosol dapsone res=
tored mucociliary transport to normal.
> CONCLUSIONS: Dapsone, given either systemically or as an aerosol, may be =
useful in treating neutrophilic airway inflammation.

Sukie (not a vet)

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"All hail the procrastinators for they shall rule the world tomorrow."
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