title: Curcumin induces human cathelicidin antimicrobial peptide gene expression through a vitamin D receptor-independent pathway.
abstract: The vitamin D receptor (VDR) mediates the pleiotropic biologic effects of 1α,25 dihydroxy-vitamin D3. Recent in vitro studies suggested that curcumin and polyunsaturated fatty acids (PUFAs) also bind to VDR with low affinity. As potential ligands for the VDR, we hypothesized that curcumin and PUFAs would induce expression of known VDR target genes in cells. In this study, we tested whether these compounds regulated two important VDR target genes - human cathelicidin antimicrobial peptide (CAMP) and 1,25-dihydroxyvitamin D3 24-hydroxylase (CYP24A1) - in human monocytic cell line U937, colon cancer cell line HT-29 and keratinocyte cell line HaCaT. We demonstrated that PUFAs failed to induce CAMP or CYP24A1 mRNA expression in all three cell lines, but curcumin up-regulated CAMP mRNA and protein levels in U937 cells. Curcumin treatment induced CAMP promoter activity from a luciferase reporter construct lacking the VDR binding site and did not increase binding of the VDR to the CAMP promoter as determined by chromatin immunoprecipitation assays. These findings indicate that induction of CAMP by curcumin occurs through a vitamin D receptor-independent manner. We conclude that PUFAs and curcumin do not function as ligands for the VDR.
authors: Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.
authors: Chunxiao
authors: C
authors: Guo
authors: Elena
authors: E
authors: Rosoha
authors: Malcolm B
authors: MB
authors: Lowry
authors: Niels
authors: N
authors: Borregaard
authors: Adrian F
authors: AF
authors: Gombart
mesh_terms: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation; D019073:HT29 Cells; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008024:Ligands; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018167:Receptors, Calcitriol / Q000235:genetics*; D015398:Signal Transduction; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism*; D020298:U937 Cells; D015854:Up-Regulation; D014807:Vitamin D / Q000031:analogs & derivatives / Q000494:pharmacology; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D005231:Fatty Acids, Unsaturated; D008024:Ligands; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D003474:Curcumin