Evidence for exclusive role of the p55 tumor necrosis factor (TNF) receptor in mediating the TNF-induced collagenase expression by human dermal fibroblasts.
The aim of this study was to examine the roles of the TNF receptors p55 and p75 in the TNF-enhanced expression of collagenase by human dermal fibroblasts. The agonistic p55 monoclonal antibody Htr9 and TNF induced production of similar amounts of collagenase. Polyclonal or monoclonal agonistic p75 antibodies failed to enhance collagenase production, and the antagonistic p75 antibody 5E12 did not inhibit TNF-enhanced expression of collagenase. This strongly suggests that p55, but not p75, is involved in TNF-induced production of collagenase. Cells continued to produce an elevated level of collagenase after the removal of TNF or Htr9. These data suggest that it may be useful to use specific inhibitors of collagenase rather than to block cytokine action directly in the treatment of diseases with chronic enhanced collagenolytic activity. A peptide of residues 36-62 of TNF previously reported to be chemotactic to leukocytes was also able to enhance the expression of collagenase activity by dermal fibroblasts. Thus, design of peptides with specific TNF effects may offer a novel approach for treatment of fibrotic disorders.
Rekdal
O
O
Department of Biotechnology, University of Tromsø, Norway.
Osterud
B
B
Svendsen
J S
JS
Winberg
J O
JO
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D017364:Collagenases / Q000378:metabolism*; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D012867:Skin / Q000166:cytology / Q000201:enzymology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D010446:Peptide Fragments; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D017364:Collagenases; D019278:Matrix Metalloproteinase 3