Inhibition of alpha-smooth muscle actin expression in an in vitro wound healing model by certain antibiotics.
OBJECTIVE
This study assesses the effects of antimicrobials on wound healing in an in vitro model of chicken flexor tendons in a collagen gel matrix. Two equidistant tendons were bathed in a culture medium for 28 days as fibroblasts (fb) grew from the tendon ends into the collagen gel and migrated toward each other until gap closure. Five groups of 10 paired tendons each included the control and the study groups, which received oxacillin (Ox), clindamycin (Cl), chloramphenicol (Chl), or tetracycline (Tet) in the culture medium to assess their effects on gap closure rate, fb migration, and myofibroblast alpha-smooth muscle (alpha-SM) actin expression.


RESULTS
Gap closure, by day 27, was 98.5% in the controls compared with 97%, 92%, 89.5%, 21.75% in the Tet, Cl, Ox, and Chl groups. Chl retarded gap closure (p < 0.05). Fb migration was similar for all groups. In the control and Ox groups, myofibroblast expressed actin at day 5. By day 7, fb cells were clearly visible in the control, Ox, and Cl groups, whereas, only light actin was present in the Chl and Tet groups. Actin band densities for the Cl, Ox, Tet, and Chl groups were 78.4%, 62.5%, 61.7% and 26.1%, respectively, of the control group.


CONCLUSIONS
These studies suggest that one reason certain antimicrobials impair wound healing, is due to myofibroblast inhibition of alpha-SM actin.
Department of Surgery at Wayne State University, Detroit, Michigan 48201, USA.
P
P
Yu
A L
AL
Vlahos
G W
GW
Dombi
A M
AM
Ledgerwood
C E
CE
Lucas
D000199:Actins / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002465:Cell Movement; D002645:Chickens; D002701:Chloramphenicol / Q000494:pharmacology; D002981:Clindamycin / Q000494:pharmacology; D046508:Culture Techniques; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005455:Fluorescent Antibody Technique; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D010068:Oxacillin / Q000494:pharmacology; D013708:Tendon Injuries / Q000503:physiopathology; D013710:Tendons / Q000166:cytology; D013752:Tetracycline / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
D000199:Actins; D000900:Anti-Bacterial Agents; D002981:Clindamycin; D002701:Chloramphenicol; D013752:Tetracycline; D010068:Oxacillin