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 p5 5 and p75 in the TNF-enhanced expression of collagenase by human derma l fibroblasts. The agonistic p55 monoclonal antibody Htr9 and TNF indu ced production of similar amounts of collagenase. Polyclonal or monocl onal 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 p7 5, is involved in TNF-induced production of collagenase. Cells continu ed to produce an elevated level of collagenase after the removal of TN F or Htr9. These data suggest that it may be useful to use specific in hibitors of collagenase rather than to block cytokine action directly in the treatment of diseases with chronic enhanced collagenolytic acti vity. A peptide of residues 36-62 of TNF previously reported to be che motactic to leukocytes was also able to enhance the expression of coll agenase activity by dermal fibroblasts. Thus, design of peptides with specific TNF effects may offer a novel approach for treatment of fibro tic disorders.