PMID- 12593855
OWN - NLM
STAT- MEDLINE
DCOM- 20030417
LR  - 20190612
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 302
IP  - 1
DP  - 2003 Feb 28
TI  - Pentoxifylline protects L929 fibroblasts from TNF-alpha toxicity via the 
      induction of heme oxygenase-1.
PG  - 109-13
AB  - Tumor necrosis factor-alpha (TNF-alpha) is recognized as a principal mediator of 
      a variety of inflammatory conditions. Pentoxifylline (PTX), which can inhibit 
      cellular TNF-alpha synthesis, also attenuates the toxic effect of TNF-alpha. 
      However, the mechanism underlying PTX-induced cytoprotection is unknown. Heme 
      oxygenase 1 (HO-1) is an enzyme which degrades heme into biliverdin, free iron, 
      and carbon monoxide (CO). This enzyme has recently been shown to have 
      anti-inflammatory and cytoprotective effects. In this study, we investigated 
      whether protection by PTX against TNF-alpha-mediated toxicity could be related to 
      its ability to induce HO-1 expression and HO activity in L929 cells. PTX in the 
      range of 0.1-1.0mM significantly induced HO-1 expression and the resulting HO 
      activity. Pre-incubation of L929 cells with either PTX or the HO activator hemin 
      resulted in the protection of the cells against TNF-alpha-mediated toxicity. Zinc 
      protoporphyrin, a specific HO competitive inhibitor, abrogated the protective 
      effect of PTX. Hemoglobin, a scavenger of CO, reversed the protective effect of 
      PTX. A cytoprotection comparable to PTX was observed when the cells were treated 
      with the CO-releasing compound tricarbonyldichlororuthenium(II) dimer. These 
      results suggest that HO-1 expression and the ensuing formation of the HO 
      metabolite CO may be a novel pathway by which PTX protects L929 cells from 
      TNF-alpha-mediated toxicity.
FAU - Oh, Gi-Su
AU  - Oh GS
AD  - Medicinal Resources Research Center (MRRC), Wonkwang University, Iksan, Chonbuk 
      570-749, Republic of Korea.
FAU - Pae, Hyun-Ock
AU  - Pae HO
FAU - Moon, Mi-Kyung
AU  - Moon MK
FAU - Choi, Byung-Min
AU  - Choi BM
FAU - Yun, Young-Gab
AU  - Yun YG
FAU - Rim, Joung-Sik
AU  - Rim JS
FAU - Chung, Hun-Taeg
AU  - Chung HT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.14.14.18 (Heme Oxygenase (Decyclizing))
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - SD6QCT3TSU (Pentoxifylline)
SB  - IM
MH  - Blotting, Western
MH  - Catalysis
MH  - Cell Line
MH  - Enzyme Induction/*drug effects
MH  - Fibroblasts/*drug effects
MH  - Heme Oxygenase (Decyclizing)/*biosynthesis
MH  - Heme Oxygenase-1
MH  - Pentoxifylline/*pharmacology
MH  - Tumor Necrosis Factor-alpha/*physiology
EDAT- 2003/02/21 04:00
MHDA- 2003/04/18 05:00
CRDT- 2003/02/21 04:00
PHST- 2003/02/21 04:00 [pubmed]
PHST- 2003/04/18 05:00 [medline]
PHST- 2003/02/21 04:00 [entrez]
AID - S0006291X03001232 [pii]
AID - 10.1016/s0006-291x(03)00123-2 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2003 Feb 28;302(1):109-13. doi: 
      10.1016/s0006-291x(03)00123-2.