PMID- 1314865
OWN - NLM
STAT- MEDLINE
DCOM- 19920528
LR  - 20190723
IS  - 0022-202X (Print)
IS  - 0022-202X (Linking)
VI  - 98
IP  - 5
DP  - 1992 May
TI  - Pentoxifylline inhibits certain constitutive and tumor necrosis 
      factor-alpha-induced activities of human normal dermal fibroblasts.
PG  - 706-12
AB  - Pentoxifylline (PFN), analog of theobromine, which phenotypically and 
      functionally alters various cell types including dermal fibroblasts, has been 
      reported to inhibit tumor necrosis factor-alpha (TNF alpha) activation of 
      neutrophils. We investigated the ability of PFN to alter constitutive and TNF 
      alpha-induced biosynthetic activities of human normal dermal fibroblasts. The 
      sixteenfold increase over constitutive intracellular 2'-5' oligo-adenylate 
      synthetase (2'-5' A synthetase) activity induced by TNF alpha (400 U/ml) failed 
      to occur when PFN (1 mg/ml) was added prior to cytokine treatment. This loss of 
      biologic activity paralleled a reduction in 2'-5' A synthetase proteins and 2'-5' 
      A synthetase-specific m-RNA. PFN failed to inhibit constitutive or TNF 
      alpha-induced IL-6 hybridoma proliferative activity, IL-6 protein, or 
      IL-6-specific m-RNA levels. The presence of PFN (1 mg/ml) in fibroblast cultures 
      reduced constitutive synthesis of collagen and glycosaminoglycan (GAG) by 87% and 
      45%, respectively, and blocked induction of their synthesis by TNF alpha (10(4) 
      U/ml). Total non-collagenous protein synthesis was not inhibited following PFN 
      treatment (1 mg/ml). PFN did not inhibit TNF alpha induction of only those 
      biosynthetic activities also susceptible to PFN in the constitutive state, with 
      PFN failing to reduce constitutive collagenolytic activity but reducing TNF 
      alpha-induced enhanced collagenolytic activity by 26% and collagenase m-RNA by 
      51%. Furthermore, PFN did inhibit, by 98%, TNF alpha-dependent murine and human 
      fibroblast cytotoxicity. The selective nature of PFN inhibition of certain TNF 
      alpha activities, the failure of PFN (1 mg/ml) to alter constitutive and TNF 
      alpha-induced levels of type 1 and 2 TNF alpha receptor m-RNA, and the finding 
      that PFN-treated fibroblasts express a similar number of receptors, of similar 
      molecular weight and high affinity for TNF alpha as control, untreated cells, 
      suggest that inhibitory activities of PFN are mediated at a locus other than 
      receptors for TNF alpha.
FAU - Berman, B
AU  - Berman B
AD  - Department of Dermatology, University of California, Davis School of Medicine.
FAU - Wietzerbin, J
AU  - Wietzerbin J
FAU - Sanceau, J
AU  - Sanceau J
FAU - Merlin, G
AU  - Merlin G
FAU - Duncan, M R
AU  - Duncan MR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (Glycosaminoglycans)
RN  - 0 (Interleukin-6)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9007-34-5 (Collagen)
RN  - EC 2.7.7.84 (2',5'-Oligoadenylate Synthetase)
RN  - EC 3.4.24.3 (Microbial Collagenase)
RN  - SD6QCT3TSU (Pentoxifylline)
SB  - IM
MH  - 2',5'-Oligoadenylate Synthetase/metabolism
MH  - Collagen/biosynthesis
MH  - Fibroblasts/drug effects/enzymology/*metabolism
MH  - Glycosaminoglycans/biosynthesis
MH  - Humans
MH  - Interleukin-6/metabolism
MH  - Microbial Collagenase/genetics
MH  - Pentoxifylline/*pharmacology
MH  - RNA, Messenger/drug effects
MH  - Receptors, Cell Surface/drug effects
MH  - Receptors, Tumor Necrosis Factor
MH  - Skin/cytology
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors
EDAT- 1992/05/01 00:00
MHDA- 1992/05/01 00:01
CRDT- 1992/05/01 00:00
PHST- 1992/05/01 00:00 [pubmed]
PHST- 1992/05/01 00:01 [medline]
PHST- 1992/05/01 00:00 [entrez]
AID - S0022-202X(92)90143-R [pii]
AID - 10.1111/1523-1747.ep12499916 [doi]
PST - ppublish
SO  - J Invest Dermatol. 1992 May;98(5):706-12. doi: 10.1111/1523-1747.ep12499916.