NDLI: Pentoxifylline downregulates α (I) collagen expression by the inhibition of Iκbα degradation in liver stellate cells

Content Provider	Springer Nature Link
Author	Hernández, E. Bucio, L. Souza, V. Escobar, M. C. Gómez Quiroz, L. E. Farfán, B. Kershebich, D. Gutiérrez Ruiz, M. C.
Copyright Year	2007
Abstract	Overproduction of collagen (I) by activated hepatic stellate cells is a critical step in the development of liver fibrosis. It has been established that these cells express interleukin (IL)-6 and respond to this cytokine with an increase in α(I) collagen. Pentoxifylline, a methylxanthine derivate, has been reported to have antifibrotic properties, but the mechanism responsible for this effect is unknown. The aim of this study was to determine the effect of pentoxifylline on acetaldehyde-induced collagen production in a rat hepatic stellate cell line (CFSC-2G cells). Cells were treated with 100 μM acetaldehyde and 200 μM pentoxifyline for 3 h. IL-6 and α(I) collagen messenger RNA (mRNA) were determined by reverse transcriptase polymerase chain reaction (RT-PCR) assay. NFκB activation was determined by electrophoretic mobility shift assay. To corroborate NFκB participation in pentoxifylline effect, cells were pretreated with 10 μM TPCK, a NFκB inhibitor. IκBα was determined by Western blot. IL-6 expression decreased significantly in acetaldehyde-pentoxifylline-treated cells. Acetaldehyde-treated cells pretreated with an anti-IL-6 monoclonal antibody did not show any increase in α (I) collagen expression. Acetaldehyde-treated cells increased 1.48 times NFκB activation, whereas acetaldehyde-pentoxifylline-treated cells decreased NFκB activation to control values. TPCK pretreated acetaldehyde cells did not present NFκB activation. To corroborate NFκB participation in pentoxifylline effect, IκBα was determined. IκBα protein level decreased 50% in acetaldehyde-treated cells, while acetaldehyde-pentoxifylline-treated cells showed IκBα control cells value. The data suggest that acetaldehyde induced α(I) collagen and IL-6 expression via NFκB activation. Pentoxifylline prevents acetaldehyde-induced α(I) collagen and IL-6 expression by a mechanism dependent on IκBα degradation, which in turn blocks NFκB activation.
Starting Page	303
Ending Page	314
Page Count	12
File Format	PDF
ISSN	07422091
Journal	Cell Biology and Toxicology
Volume Number	24
Issue Number	4
e-ISSN	15736822
Language	English
Publisher	Springer Netherlands
Publisher Date	2007-10-20
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	α (I) collagen HSC IκB IL-6 Liver fibrosis NFκB Pentoxifylline Biochemistry Pharmacology/Toxicology Cell Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Health, Toxicology and Mutagenesis Toxicology

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