Reversal of second-hand cigarette smoke-induced impairment of corneal wound healing by thymosin beta4 combined with anti-inflammatory agents.
OBJECTIVE
Abnormalities in corneal reepithelialization caused by second-hand cigarette smoke (CS) are less known than the effects of CS on other tissues. The effects of CS on corneal epithelial cell migration and associated signaling mechanisms were examined, to determine the mechanisms by which CS delays corneal wound healing.


METHODS
Corneal epithelial cells in two-dimensional or organ culture were exposed to sidestream whole (SSW) smoke, a major component of second-hand CS. Thymosin beta 4 (Tbeta4), a molecule thought to promote wound healing in the cornea, was tested to determine whether it can reverse the adverse effects of SSW smoke on corneal healing.


RESULTS
Cell migration, actin reorganization, and phosphorylation of focal adhesion kinase (FAK) and paxillin were all inhibited by exposure to SSW smoke, and the distribution of phospho-src in the cells was disrupted. Activation of RhoA, an important regulator of the cytoskeleton during cell migration, was also inhibited. Tbeta4 stimulated corneal epithelial cell migration in the presence of SSW smoke in culture and in vivo, and it partially reversed the inhibition of corneal healing by SSW smoke. However, Tbeta4 plus dexamethasone, an inhibitor of inflammation, together, reversed the effects of SSW smoke on corneal healing.


CONCLUSIONS
These findings suggest that SSW smoke exerts its effects on cell migration during corneal epithelial healing through inhibition of actin reorganization, activation of focal adhesion molecules, formation of the focal adhesion complex, and activation of Rho-GTPases. Furthermore, they strongly suggest that corneal injury induced by toxicants can be treated using anti-inflammatory agents coupled with Tbeta4.
Yuan
Hongwei
H
Department of Cell Biology and Neuroscience, University of California, Riverside, CA 92521, USA.
Ma
Chongze
C
Moinet
Lisa
L
Sato
Noboru
N
Martins-Green
Manuela
M
D000199:Actins / Q000378:metabolism; D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005131:Eye Injuries / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009924:Organ Culture Techniques; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D013947:Thymosin / Q000008:administration & dosage*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014945:Wound Healing / Q000187:drug effects*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000099201:Thymosin beta(4)
D000199:Actins; D000893:Anti-Inflammatory Agents; D003907:Dexamethasone; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051419:Paxillin; D013947:Thymosin; D014028:Tobacco Smoke Pollution; D020742:rhoA GTP-Binding Protein; D000099201:Thymosin beta(4); C496061:PXN protein, human