B lymphocyte-induced maturation protein 1 is a novel target gene of aryl hydrocarbon receptor.
BACKGROUND
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor. When environmental pollutants, including chemical carcinogens, bind to AhR, the receptor translocates to nucleus and transcriptionally activates target genes including drug metabolizing enzymes such as P450s. Recent studies have shown that AhR mediates various responses, including cellular growth, differentiation, immune system and development.


OBJECTIVE
In this study, we investigated the physiological function of AhR in skin.


METHODS
Distribution of AhR in murine skin was examined by immunohistochemistry. Expression of a target gene which is transcriptionally activated by AhR is analysed by RT-PCR.


RESULTS
We found that AhR co-localizes with the transcriptional repressor B lymphocyte maturation protein 1 (Blimp1) in sebaceous gland. In this report, we show that expression of Blimp1 is induced by treatment with AhR ligands, such as methylcolanthrene (MC) in sebocyte and keratinocyte cell lines. Exposure to ultraviolet B, which has been reported to generate AhR ligand intracellularly, also increased Blimp1 mRNA. This ligand-dependent induction of Blimp1 requires the expression of both AhR and ARNT, since transfection of siRNA specific to either AhR or ARNT significantly reduced Blimp1 mRNA in response to MC. Analysis using kinase inhibitors revealed that ligand-dependent induction of Blimp1, but not that of CYP1A1, is inhibited by staurosporine. TPA, a potent activator of protein kinase C, increased Blimp1 mRNA but not CYP1A1.


CONCLUSIONS
These data indicate that Blimp1 is a novel AhR-target gene in epidermal keratinocyte and sebocyte.
Ikuta
Togo
T
Research Institute for Clinical Oncology, Saitama Cancer Center, 818 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806, Japan. togo@cancer-c.pref.saitama.jp
Ohba
Motoi
M
Zouboulis
Christos C
CC
Fujii-Kuriyama
Yoshiaki
Y
Kawajiri
Kaname
K
D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000502:physiology; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics* / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012627:Sebaceous Glands / Q000166:cytology / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology
C497396:ARNT protein, human; C497397:Arnt protein, mouse; D004791:Enzyme Inhibitors; C513258:Prdm1 protein, mouse; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018336:Receptors, Aryl Hydrocarbon; D012097:Repressor Proteins; D014157:Transcription Factors; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1; D019311:Staurosporine