Effect of interferon-alpha2b on XXXX wound closure and the expression of cytoskeletal proteins in vivo.

@entity1885 @entity964 @entity5 @entity840 @entity1977 @entity74 @entity2805 @entity130 @entity2472
Scar contraction following the healing of deep partial-thickness or full-thickness @entity130 is a leading cause of functional and cosmetic morbidity. The therapeutic use of interferon for the treatment of @entity74 associated with @entity2472 , including @entity2805 , has been suggested because of its antifibrotic properties. Treatment of fibroblasts with interferon has been shown to reduce the rate and extent of contraction using the in vitro fibroblast-populated collagen lattice model. In order to establish the effect of interferon-alpha2b on full-thickness wound contraction in vivo, osmotic pumps loaded with interferon or sterile saline were implanted intraperitoneally in @entity840 . Seven days following implantation, six full-thickness punch biopsy wounds were created and were monitored by daily assessment of the wound. There was a significant reduction in the rate of wound contraction in the interferon-treated animals after day 3 (p < 0.01). Western blot analysis was used to quantitate selected cytoskeletal proteins in the normal skin and tissue biopsied from the wound at days 7, 14, and 21 postinjury. The amount of @entity964 in the contracted wound @entity130 as compared with the amount present in normal skin (p < 0.0001); however, the relative amounts of the myofibroblast-associated cytoskeletal proteins alpha-smooth muscle actin and smooth muscle myosin were less than those found in normal, uninjured skin. By using @entity964 to adjust the levels of cytoskeletal proteins for the increase in cellularity in the wounds, both alpha-smooth muscle actin and smooth muscle myosin significantly increased after closure of the wounds on day 14, as compared with the @entity5 (day 7), before further reductions occurred with remodeling on day 21. Measurement of apoptotic cells using the terminal deoxynucleotidyl transferase-mediated @entity1977 - @entity1885 nick end labeling assay revealed an increase in apoptosis in the interferon-alpha2b-treated animals at 21 days following wounding (p < 0.001), which did not colocalize with alpha-smooth muscle actin staining. Taken together, these findings suggest that interferon-alpha2b inhibits wound contraction in vivo, not through an appreciable alteration in myofibroblast number or cytoskeletal protein expression, but possibly through a reduction in fibroblast cellularity by the induction of apoptosis.
