PMID- 7636301
OWN - NLM
STAT- MEDLINE
DCOM- 19950912
LR  - 20190723
IS  - 0022-202X (Print)
IS  - 0022-202X (Linking)
VI  - 105
IP  - 2
DP  - 1995 Aug
TI  - TNF-R55-specific form of human tumor necrosis factor-alpha induces collagenase 
      gene expression by human skin fibroblasts.
PG  - 197-202
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a potent inhibitor of connective 
      tissue formation. The cellular effects of TNF-alpha are mediated by two distinct 
      cell-surface receptors, TNF-R55 and TNF-R75, both present on various types of 
      cells, including fibroblasts. In this study we wanted to elucidate the role of 
      TNF-R55 as a mediator of the connective tissue effects of TNF-alpha by using a 
      mutant, TNF-R55-specific form of human TNF-alpha. This mutant TNF-alpha markedly 
      induced collagenase and stromelysin-1 gene expression in dermal fibroblasts, the 
      maximal activation (up to 42-fold) being 65%-89% of that noted with wild-type 
      human TNF-alpha. In addition, TNF-R55-specific TNF-alpha suppressed type I 
      collagen mRNA levels as potently as wild-type TNF-alpha (by 60%). The enhancement 
      of collagenase gene expression by TNF-R55-specific TNF-alpha was augmented by 
      simultaneous treatment of normal and scleroderma skin fibroblasts with 
      interferon-gamma, indicating specific enhancement of TNF-R55 signaling pathway by 
      interferon-gamma. These results show that stimulation of the TNF-R55 signaling 
      pathway is sufficient for the inhibitory effects of TNF-alpha on extracellular 
      matrix formation by dermal fibroblasts. It is conceivable that due to reduced 
      systemic toxicity, TNF-R55-specific forms of human TNF-alpha may prove to be 
      feasible in the therapy of fibrotic disorders.
FAU - Westermarck, J
AU  - Westermarck J
AD  - Department of Medical Biochemistry, University of Turku, Finland.
FAU - Hakkinen, L
AU  - Hakkinen L
FAU - Fiers, W
AU  - Fiers W
FAU - Kahari, V M
AU  - Kahari VM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (Antigens, CD)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.4.24.- (Collagenases)
SB  - IM
MH  - Adult
MH  - Antigens, CD/*physiology
MH  - Cells, Cultured
MH  - Collagenases/*genetics
MH  - Fibroblasts/physiology
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Interferon-gamma/pharmacology
MH  - Male
MH  - RNA, Messenger/metabolism
MH  - Receptors, Tumor Necrosis Factor/*physiology
MH  - Receptors, Tumor Necrosis Factor, Type I
MH  - Scleroderma, Systemic/pathology
MH  - Skin/cytology
MH  - *Skin Physiological Phenomena
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1995/08/01 00:00
MHDA- 1995/08/01 00:01
CRDT- 1995/08/01 00:00
PHST- 1995/08/01 00:00 [pubmed]
PHST- 1995/08/01 00:01 [medline]
PHST- 1995/08/01 00:00 [entrez]
AID - S0022-202X(15)42277-8 [pii]
AID - 10.1111/1523-1747.ep12317114 [doi]
PST - ppublish
SO  - J Invest Dermatol. 1995 Aug;105(2):197-202. doi: 10.1111/1523-1747.ep12317114.