VDR and MEK-ERK dependent induction of the antimicrobial peptide cathelicidin in keratinocytes by lithocholic acid.
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.
Peric
Mark
M
Department of Dermatology and Allergy, Ludwig-Maximilians-University, Munich, Germany.
Koglin
Sarah
S
Dombrowski
Yvonne
Y
Gross
Kathrin
K
Bradac
Eva
E
Ruzicka
Thomas
T
Schauber
Jürgen
J
D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis* / Q000276:immunology; D018938:Caco-2 Cells; D002117:Calcitriol / Q000494:pharmacology* / Q000627:therapeutic use; D003902:Detergents / Q000494:pharmacology* / Q000627:therapeutic use; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism*; D008095:Lithocholic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D020930:MAP Kinase Kinase Kinases / Q000276:immunology / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000276:immunology / Q000302:isolation & purification; D012871:Skin Diseases / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D014815:Vitamins / Q000494:pharmacology* / Q000627:therapeutic use; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; D003902:Detergents; D012333:RNA, Messenger; D014815:Vitamins; D008095:Lithocholic Acid; D020930:MAP Kinase Kinase Kinases; D002117:Calcitriol; D054804:Cathelicidins