VDR and MEK-ERK dependent induction of the antimicrobial peptide cathelicidin in keratinocytes by lithocholic acid

Mark Peric; Sarah Koglin; Yvonne Dombrowski; Kathrin Gross; Eva Bradac; Thomas Ruzicka; Jürgen Schauber

doi:10.1016/j.molimm.2009.08.010

VDR and MEK-ERK dependent induction of the antimicrobial peptide cathelicidin in keratinocytes by lithocholic acid

Mark Peric, Sarah Koglin, Yvonne Dombrowski, Kathrin Gross, Eva Bradac, Thomas Ruzicka, Jürgen Schauber

School of Medicine, Dentistry and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

31 Citations (Scopus)

Abstract

Cathelicidin is an antimicrobial peptide (AMP) and signaling molecule in innate immunity and a direct target of 1,25-dihydroxyvitamin D3 (1,25D3) in primary human keratinocytes (NHEK). The expression of cathelicidin is dysregulated in various skin diseases and its regulation differs depending on the epithelial cell type. The secondary bile acid lithocholic acid (LCA) is a ligand of the vitamin D receptor (VDR) and can carry out in vivo functions of vitamin D3. Therefore we analyzed cathelicidin mRNA- and peptide expression levels in NHEK and colonic epithelial cells (Caco-2) after stimulation with LCA. We found increased expression of cathelicidin mRNA and peptide in NHEK, in Caco-2 colon cells no effect was observed after LCA stimulation. The VDR as well as MEK-ERK signaled the upregulation of cathelicidin in NHEK induced by LCA. Collectively, our data indicate that cathelicidin induction upon LCA treatment differs in keratinocytes and colonic epithelial cells. Based on these observations LCA-like molecules targeting cathelicidin could be designed for the treatment of cutaneous diseases that are characterized by disturbed cathelicidin expression.

Original language	English
Pages (from-to)	3183-3187
Number of pages	5
Journal	Molecular Immunology
Volume	46
Issue number	16
Early online date	05 Sept 2009
DOIs	https://doi.org/10.1016/j.molimm.2009.08.010
Publication status	Published - Oct 2009

Keywords

Antimicrobial Cationic Peptides
Caco-2 Cells
Calcitriol
Detergents
Enzyme Activation
Gene Expression Regulation
Humans
Keratinocytes
Lithocholic Acid
MAP Kinase Kinase Kinases
MAP Kinase Signaling System
RNA, Messenger
Skin Diseases
Vitamins

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.molimm.2009.08.010

http://www.sciencedirect.com/science/article/pii/S0161589009006841

Cite this

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title = "VDR and MEK-ERK dependent induction of the antimicrobial peptide cathelicidin in keratinocytes by lithocholic acid",

abstract = "Cathelicidin is an antimicrobial peptide (AMP) and signaling molecule in innate immunity and a direct target of 1,25-dihydroxyvitamin D3 (1,25D3) in primary human keratinocytes (NHEK). The expression of cathelicidin is dysregulated in various skin diseases and its regulation differs depending on the epithelial cell type. The secondary bile acid lithocholic acid (LCA) is a ligand of the vitamin D receptor (VDR) and can carry out in vivo functions of vitamin D3. Therefore we analyzed cathelicidin mRNA- and peptide expression levels in NHEK and colonic epithelial cells (Caco-2) after stimulation with LCA. We found increased expression of cathelicidin mRNA and peptide in NHEK, in Caco-2 colon cells no effect was observed after LCA stimulation. The VDR as well as MEK-ERK signaled the upregulation of cathelicidin in NHEK induced by LCA. Collectively, our data indicate that cathelicidin induction upon LCA treatment differs in keratinocytes and colonic epithelial cells. Based on these observations LCA-like molecules targeting cathelicidin could be designed for the treatment of cutaneous diseases that are characterized by disturbed cathelicidin expression.",

keywords = "Antimicrobial Cationic Peptides, Caco-2 Cells, Calcitriol, Detergents, Enzyme Activation, Gene Expression Regulation, Humans, Keratinocytes, Lithocholic Acid, MAP Kinase Kinase Kinases, MAP Kinase Signaling System, RNA, Messenger, Skin Diseases, Vitamins",

author = "Mark Peric and Sarah Koglin and Yvonne Dombrowski and Kathrin Gross and Eva Bradac and Thomas Ruzicka and J{\"u}rgen Schauber",

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pages = "3183--3187",

journal = "Molecular Immunology",

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T1 - VDR and MEK-ERK dependent induction of the antimicrobial peptide cathelicidin in keratinocytes by lithocholic acid

AU - Peric, Mark

AU - Koglin, Sarah

AU - Dombrowski, Yvonne

AU - Gross, Kathrin

AU - Bradac, Eva

AU - Ruzicka, Thomas

AU - Schauber, Jürgen

PY - 2009/10

Y1 - 2009/10

N2 - Cathelicidin is an antimicrobial peptide (AMP) and signaling molecule in innate immunity and a direct target of 1,25-dihydroxyvitamin D3 (1,25D3) in primary human keratinocytes (NHEK). The expression of cathelicidin is dysregulated in various skin diseases and its regulation differs depending on the epithelial cell type. The secondary bile acid lithocholic acid (LCA) is a ligand of the vitamin D receptor (VDR) and can carry out in vivo functions of vitamin D3. Therefore we analyzed cathelicidin mRNA- and peptide expression levels in NHEK and colonic epithelial cells (Caco-2) after stimulation with LCA. We found increased expression of cathelicidin mRNA and peptide in NHEK, in Caco-2 colon cells no effect was observed after LCA stimulation. The VDR as well as MEK-ERK signaled the upregulation of cathelicidin in NHEK induced by LCA. Collectively, our data indicate that cathelicidin induction upon LCA treatment differs in keratinocytes and colonic epithelial cells. Based on these observations LCA-like molecules targeting cathelicidin could be designed for the treatment of cutaneous diseases that are characterized by disturbed cathelicidin expression.

AB - Cathelicidin is an antimicrobial peptide (AMP) and signaling molecule in innate immunity and a direct target of 1,25-dihydroxyvitamin D3 (1,25D3) in primary human keratinocytes (NHEK). The expression of cathelicidin is dysregulated in various skin diseases and its regulation differs depending on the epithelial cell type. The secondary bile acid lithocholic acid (LCA) is a ligand of the vitamin D receptor (VDR) and can carry out in vivo functions of vitamin D3. Therefore we analyzed cathelicidin mRNA- and peptide expression levels in NHEK and colonic epithelial cells (Caco-2) after stimulation with LCA. We found increased expression of cathelicidin mRNA and peptide in NHEK, in Caco-2 colon cells no effect was observed after LCA stimulation. The VDR as well as MEK-ERK signaled the upregulation of cathelicidin in NHEK induced by LCA. Collectively, our data indicate that cathelicidin induction upon LCA treatment differs in keratinocytes and colonic epithelial cells. Based on these observations LCA-like molecules targeting cathelicidin could be designed for the treatment of cutaneous diseases that are characterized by disturbed cathelicidin expression.

KW - Antimicrobial Cationic Peptides

KW - Caco-2 Cells

KW - Calcitriol

KW - Detergents

KW - Enzyme Activation

KW - Gene Expression Regulation

KW - Humans

KW - Keratinocytes

KW - Lithocholic Acid

KW - MAP Kinase Kinase Kinases

KW - MAP Kinase Signaling System

KW - RNA, Messenger

KW - Skin Diseases

KW - Vitamins

U2 - 10.1016/j.molimm.2009.08.010

DO - 10.1016/j.molimm.2009.08.010

M3 - Article

C2 - 19733911

SN - 0161-5890

VL - 46

SP - 3183

EP - 3187

JO - Molecular Immunology

JF - Molecular Immunology

IS - 16

ER -

VDR and MEK-ERK dependent induction of the antimicrobial peptide cathelicidin in keratinocytes by lithocholic acid

Abstract

Keywords

UN SDGs

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