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http://purl.uniprot.org/citations/20970965http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20970965http://www.w3.org/2000/01/rdf-schema#comment"

Background

Production of antimicrobial peptides (AMPs) is the primary mechanism by which skin innate immunity protects against infection. Hormonally active vitamin D3 (1α,25-dihydroxyvitamin D3; 1,25D₃) is a vital regulator of skin innate immunity, and has been shown to increase the expression and function of AMPs.

Objective

PPARγ is a ligand-activated nuclear receptor and plays a role in keratinocyte differentiation and cutaneous homeostasis. In this study, we investigate whether 1,25D₃-activated PPARγ signaling regulates AMP expression in keratinocytes.

Methods

Subconfluent keratinocytes were treated with 1,25D₃ for the indicated times. The mRNA and protein levels of AMPs were detected by RT-PCR and Western blot, and the DNA binding activation of PPARγ, VDRE and AP-1 was investigated by EMSA. To examine the role of PPARγ, the recombinant adenovirus carrying a dominant-negative form of PPARγ (dn-PPARγ) was constructed and transfected into keratinocytes.

Results

We show here that 1,25D₃ significantly enhances hBD-3 and cathelicidin expression in keratinocytes. Expression of dn-PPARγ did not affect binding to the vitamin D-responsive element (VDRE), which is crucial for cathelicidin induction by VD3; however, it did decrease 1,25D₃ induction of both hBD-3 and cathelicidin. Inhibition of the p38, ERK, and JNK signaling pathways blocked hBD-3 expression, whereas only p38 inhibition suppressed cathelicidin induction. dn-PPARγ had no effect on ERK and JNK activity, but inhibited p38 phosphorylation and suppressed 1,25D₃-induced AP-1 activation via effects on Fra1 and c-Fos proteins.

Conclusions

In conclusion, PPARγ regulates the 1,25D₃-induced hBD-3 and cathelicidin expression in keratinocytes through the regulation of AP-1 and p38 activity."xsd:string
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http://purl.uniprot.org/citations/20970965http://purl.uniprot.org/core/author"Dai X."xsd:string
http://purl.uniprot.org/citations/20970965http://purl.uniprot.org/core/author"Hashimoto K."xsd:string
http://purl.uniprot.org/citations/20970965http://purl.uniprot.org/core/author"Yang L."xsd:string
http://purl.uniprot.org/citations/20970965http://purl.uniprot.org/core/author"Tohyama M."xsd:string
http://purl.uniprot.org/citations/20970965http://purl.uniprot.org/core/author"Shirakata Y."xsd:string
http://purl.uniprot.org/citations/20970965http://purl.uniprot.org/core/author"Hirakawa S."xsd:string
http://purl.uniprot.org/citations/20970965http://purl.uniprot.org/core/author"Hanakawa Y."xsd:string
http://purl.uniprot.org/citations/20970965http://purl.uniprot.org/core/author"Sayama K."xsd:string
http://purl.uniprot.org/citations/20970965http://purl.uniprot.org/core/author"Tokumaru S."xsd:string
http://purl.uniprot.org/citations/20970965http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20970965http://purl.uniprot.org/core/name"J Dermatol Sci"xsd:string
http://purl.uniprot.org/citations/20970965http://purl.uniprot.org/core/pages"179-186"xsd:string
http://purl.uniprot.org/citations/20970965http://purl.uniprot.org/core/title"PPARgamma mediates innate immunity by regulating the 1alpha,25-dihydroxyvitamin D3 induced hBD-3 and cathelicidin in human keratinocytes."xsd:string
http://purl.uniprot.org/citations/20970965http://purl.uniprot.org/core/volume"60"xsd:string
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