Differential effects of pentoxifylline on the hepatic inflammatory response in porcine liver cell cultures - Increase in inducible nitric oxide synthase expression
Khn. Hoebe et al., Differential effects of pentoxifylline on the hepatic inflammatory response in porcine liver cell cultures - Increase in inducible nitric oxide synthase expression, BIOCH PHARM, 61(9), 2001, pp. 1137-1144
Pentoxifylline (PTX) has been shown to exert hepatoprotective effects in va
rious liver injury models. However, little information is available about t
he effect of PTX on the hepatic acute phase response. In the present study,
the effect of PTX on a lipopolysaccharide (LPS)-induced acute phase respon
se in primary porcine liver cell cultures was examined. During 72 hr of inc
ubation with or without LPS, the ability of PTX to influence the secretion
of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), acute ph
ase proteins, and nitric oxide (NO) was assessed. PTX completely inhibited
LPS-induced TNF-alpha production and attenuated IL-6 only after 48 hr of in
cubation. In contrast, PTX potentiated NO production and the expression of
inducible nitric oxide synthase (NOS) in hepatocytes after stimulation with
LPS, The increased expression of iNOS and concurrent production of NO was
also observed when liver cell cultures were incubated with dibutyryl cyclic
adenosine monophosphate. No effect of PTX on acute phase protein secretion
was observed during 72 hr of incubation. The present results show that PTX
differentially affects the endotoxin-induced inflammatory response in prim
ary porcine liver cell cultures by suppressing TNF-alpha and IL-6 while pot
entiating NO production. (C) 2001 Elsevier Science Inc. All rights reserved
.