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Vol. 293, Issue 1, 82-90, April 2000
B in Mice1,2
Department of Molecular Biosciences, School of Veterinary Medicine,
University of California, Davis, California
The effects of taurine (T) and niacin (N) on bleomycin (BL)-induced
increased production of tumor necrosis factor-
(TNF-
), interleukin (IL)-1
, IL-6, and transforming growth factor-
(TGF-
) levels in the bronchoalveolar lavage fluid (BALF), and
increased collagen content and nuclear factor-
B (NF-
B) activation
in the lungs were investigated in mice. The mice were intratracheally instilled with saline (SA) or BL (0.1 U/mouse/50 µl) under ketamine and xylazine anesthesia. They had ad libitum access to diet containing 2.5% niacin (w/w) or the same control diet (CD) and water with and
without taurine (1%) 3 days before intratracheal instillation and
throughout the study. The mice were sacrificed at different times for
collecting BALF and lungs, which were appropriately processed for
various measurements. Treatment with taurine and niacin attenuated the
BL-induced increases in proinflammatory cytokines such as IL-1
,
TNF-
, IL-6, and TGF-
in BALF and lung hydroxyproline content of
the mice in BL + TN groups. Reverse transcription-polymerase chain
reaction analysis of total RNA from whole lung was performed to assess
the induction of TNF-
and IL-1 mRNAs as markers of NF-
B
activation. The NF-
B DNA-binding activity in whole-lung extract was
evaluated by electrophoretic mobility shift assay. This revealed a
progressive increase in NF-
B activation and IkB
depletion in
lungs from mice in BL + CD groups from day 1 through day 21 compared
with the corresponding SA + CD control groups. Treatment with taurine
and niacin generally inhibited the BL-induced increases in the nuclear
localization of NF-
B and preserved I
B
protein in BL + TN
groups. This may be one of the mechanisms for the antifibrotic effect
of taurine and niacin.
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