Role of NF-kappaB in constitutive expression of MAIL in epidermal keratinocytes.
Molecule possessing ankyrin-repeats induced by lipopolysaccharide (MAIL) is a nuclear IkappaB protein that is also known as interleukin-1-inducible nuclear ankyrin repeat protein and inhibitor of nuclear factor kappaBzeta (IkappaBzeta). We previously observed that MAIL-deficient mice were affected by atopic dermatitis-like skin lesions and demonstrated the importance of MAIL in the skin. In this study, we investigated MAIL expression in mouse keratinocytes. MAIL mRNA was constitutively expressed in the skin epidermis. MAIL expression was also confirmed in primary keratinocytes and the PAM212 keratinocyte cell line. The inhibitors of nuclear factor kappaB (NF-kappaB)-Bay11-7082 and the IkappaBalphaM supersuppressor-considerably downregulated MAIL expression in the keratinocytes. Immunoreactivity for NF-kappaB components was localized in the cytoplasm and nucleus of normal unstimulated keratinocytes. The expression level of MAIL in the skin did not change following lipopolysaccharide (LPS) administration to mice. Interestingly, in accordance with the in vivo findings, the MAIL expression level did not change following LPS stimulation even in primary keratinocytes; however, MAIL expression was strongly increased by interleukin-1 stimulation. These results collectively suggest that the constitutive expression of MAIL in keratinocytes is controlled, at least in part, by NF-kappaB and that there may be LPS-specific repressive mechanisms that inhibit MAIL induction.
Oonuma
Toshina
T
United Graduate School of Veterinary Science, Gifu University, Japan.
Morimatsu
Masami
M
Ochiai
Kazuhiko
K
Iwanaga
Toshihiko
T
Hashizume
Kazuyoshi
K
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002460:Cell Line; D017931:DNA Primers; D007150:Immunohistochemistry; D007375:Interleukin-1; D015603:Keratinocytes / Q000378:metabolism*; D008070:Lipopolysaccharides; D008156:Luciferases; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; D007375:Interleukin-1; D008070:Lipopolysaccharides; D016328:NF-kappa B; C485947:Nfkbiz protein, mouse; D009687:Nuclear Proteins; D008156:Luciferases