Histone acetylation in Keratinocytes enables control of the expression of cathelicidin and CD14 by 1,25-dihydroxyvitamin D3

被引:116
作者
Schauber, Juergen [1 ,2 ,3 ]
Oda, Yuko [4 ]
Buechau, Amanda S. [1 ,2 ]
Yun, Qian-Chun [6 ]
Steinmeyer, Andreas [5 ]
Zuegel, Ulrich [7 ]
Bikle, Daniel D. [4 ]
Gallo, Richard L. [1 ,2 ]
机构
[1] Univ Calif San Diego, Div Dermatol, San Diego, CA 92103 USA
[2] VA San Diego Healthcare Syst, San Diego, CA 92103 USA
[3] Univ Munich, Dept Dermatol, D-8000 Munich, Germany
[4] Univ Calif San Diego, Vet Affairs Med Ctr, Dept Med, Endocrine Unit, San Diego, CA 92161 USA
[5] Bayer Schering Pharma AG, Berlin, Germany
[6] Univ Penn, Sch Med, Philadelphia, PA 19104 USA
[7] Bayer Schering Pharma AG, Therapeut Res Grp Inflammat & Immunol Global Drug, Berlin, Germany
关键词
D O I
10.1038/sj.jid.5701102
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Hormonally active vitamin D-3 - 1,25- dihydroxyvitamin D-3 ( 1,25D3) - acts as a signaling molecule in cutaneous immunity by increasing pattern recognition through Toll- like receptor- 2 ( TLR2), and increasing the expression and function of antimicrobial peptides. Here we show that the actions of 1,25D3 on keratinocyte innate immune responses are influenced by histone acetylation and require the steroid receptor coactivator 3 ( SRC3), which mediates inherent histone acetyltransferase ( HAT) activity. SRC3 was detected in the suprabasal and granular layer of the skin, similar to cathelicidin expression. HAT activity was important to keratinocyte cathelicidin expression as the combination of histone deacetylase inhibitors ( HDACi) ( butyrate or trichostatin A) and 1,25D3 increased cathelicidin and CD14 expression and enhanced the antimicrobial function of keratinocytes against Staphylococcus aureus. This treatment, or activation of TLR2, also directly increased acetylation of histone 4. Small interfering RNA silencing of the vitamin D receptor or SRC3 blocked the induction of cathelicidin and CD14 by 1,25D3. HDACi could not reverse this effect or influence cathelicidin in the absence of 1,25D3, suggesting that both are necessary for function. These studies demonstrate that the epigenetic control of gene transcription by histone acetylation is important for 1,25D3- regulated antimicrobial and TLR function of keratinocytes, essential elements of the innate immune response of the skin.
引用
收藏
页码:816 / 824
页数:9
相关论文
共 31 条
[1]   An injected bacterial effector targets chromatin access for transcription factor NF-κB to alter transcription of host genes involved in immune responses [J].
Arbibe, Laurence ;
Kim, Dong Wook ;
Batsche, Eric ;
Pedron, Thierry ;
Mateescu, Bogdan ;
Muchardt, Christian ;
Parsot, Claude ;
Sansonetti, Philippe J. .
NATURE IMMUNOLOGY, 2007, 8 (01) :47-56
[2]   Wavelength-dependent induction of CYP24A1-mRNA after UVB-triggered calcitriol synthesis in cultured human keratinocytes [J].
Baer, Michael ;
Domaschke, Doerte ;
Meye, Axel ;
Lehmann, Bodo ;
Meurer, Michael .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2007, 127 (01) :206-213
[3]   Vitamin D regulated keratinocyte differentiation [J].
Bikle, DD .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2004, 92 (03) :436-444
[4]   Histone deacetylase activities are required for innate immune cell control of Th1 but not Th2 effector cell function [J].
Brogdon, Jennifer L. ;
Xu, Yongyao ;
Szabo, Susanne J. ;
An, Shaojian ;
Buxton, Francis ;
Cohen, Dalia ;
Huang, Qian .
BLOOD, 2007, 109 (03) :1123-1130
[5]   Regulation of human epidermal keratinocyte differentiation by the vitamin D receptor and its coactivators DRIP205, SRC2, and SRC3 [J].
Hawker, Nathaniel P. ;
Pennypacker, Sally D. ;
Chang, Sandra M. ;
Bikle, Daniel D. .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2007, 127 (04) :874-880
[6]   Successful treatment of refractory warts with topical vitamin D3 derivative (maxacalcitol, 1α, 25-dihydroxy-22-oxacalcitriol) in 17 patients [J].
Imagawa, Ichiro ;
Suzuki, Hiroyuki .
JOURNAL OF DERMATOLOGY, 2007, 34 (04) :264-266
[7]   Downregulation of bactericidal peptides in enteric infections: A novel immune escape mechanism with bacterial DNA as a potential regulator [J].
Islam, D ;
Bandholtz, L ;
Nilsson, J ;
Wigzell, H ;
Christensson, B ;
Agerberth, B ;
Gudmundsson, GH .
NATURE MEDICINE, 2001, 7 (02) :180-185
[8]   Focus on acetylation: the role of histone deacetylase inhibitors in cancer therapy and beyond [J].
Konstantinopoulos, Panagiotis A. ;
Karamouzis, Michalis V. ;
Papavassiliou, Athanasios G. .
EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2007, 16 (05) :569-571
[9]   Antagonist- and inverse agonist-driven interactions of the vitamin D receptor and the constitutive androstane receptor with corepressor protein [J].
Lempiäinen, H ;
Molnár, F ;
Gonzalez, MM ;
Peräkylä, M ;
Carlberg, C .
MOLECULAR ENDOCRINOLOGY, 2005, 19 (09) :2258-2272
[10]   The SRC family of nuclear receptor coactivators [J].
Leo, C ;
Chen, JD .
GENE, 2000, 245 (01) :1-11