I?B kinase ? regulates epithelium migration during corneal wound healing.

ABSTRACT: The IKK? is known to regulate transcription factor NF-?B activation leading to inflammatory responses. Recent gene knockout studies have shown that IKK? can orchestrate local inflammatory responses and regulate homeostasis of epithelial tissues. To investigate whether IKK? has an intrinsic role in epithelial cells, we established an in vivo system in the immune privileged corneal epithelium. We generated triple transgenic Krt12(rtTA/rtTAt)/tet-O-Cre/Ikk?(F/F) (Ikk?(?CE/?CE)) mice by crossing the Krt12-rtTA knock-in mice, which express the reverse tetracycline transcription activator in corneal epithelial cells, with the tet-O-Cre and Ikk?(F/F) mice. Doxycycline-induced IKK? ablation occurred in corneal epithelial cells of triple transgenic Ikk?(?CE/?CE) mice, but loss of IKK? did not cause ocular abnormalities in fetal development and postnatal maintenance. Instead, loss of IKK? significantly delayed healing of corneal epithelial debridement without affecting cell proliferation, apoptosis or macrophage infiltration. In vitro studies with human corneal epithelial cells (HCEpi) also showed that IKK? was required for cytokine-induced cell migration and wound closure but was dispensable for cell proliferation. In both in vivo and in vitro settings, IKK? was required for optimal activation of NF-?B and p38 signaling in corneal epithelial cells, and p38 activation is likely mediated through formation of an IKK?-p38 protein complex. Thus, our studies in corneal epithelium reveal a previously un-recognized role for IKK? in the control of epithelial cell motility and wound healing.

SUBMITTER: Chen L 

PROVIDER: S-EPMC3022035 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature