title: Vitamin D3 modulates the innate immune response through regulation of the hCAP-18/LL-37 gene expression and cytokine production.
abstract: BACKGROUND
  The steroid hormone metabolite of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25D3), promotes osteogenic activity and regulates calcium and phosphate metabolism, which are actions regarded as classical vitamin D-regulated functions. Besides its role in these processes, 1,25D3 also seems implicated in the host defense against microbial/pro-inflammatory attacks. Low serum levels of vitamin D3 (vitamin D deficiency) are associated with osteoporosis and increased risk of fractures but also inflammatory diseases and their disease progression, presumably via mechanisms associated with 1,25D3-evoked modulation of the innate immune system. 1,25D3 has been reported to modulate many inflammatory responses, suggesting that it regulates multiple transcriptional targets within the inflammatory system.
  
  
  RESULTS
  Experimental studies in various experimental systems show that 1,25D3 differentially regulates the production of pro-inflammatory cytokines and chemokines depending on cell type. Importantly, many reports show that 1,25D3 up-regulates expression of the human antimicrobial peptide hCAP-18/LL-37 gene. The hCAP-18/LL-37 gene seems indeed to be an important transcriptional target for 1,25D3. However, only limited evidence is presented showing that 1,25D3 consistently increases the amount of biologically active LL-37 peptide.
  
  
  CONCLUSIONS
  In the present review, we discuss 1,25D3-induced down-regulation of cytokine/chemokine production and stimulation of hCAP-18/LL-37 gene expression which represent two very important pathways for 1,25D3-evoked regulation of the innate immune response.
authors.affiliation: Department of Experimental Medical Science, Lund University, BMC D12, 221 84, Lund, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Svensson
authors.affiliation: Department of Experimental Medical Science, Lund University, BMC D12, 221 84, Lund, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Nebel
authors.affiliation: Department of Experimental Medical Science, Lund University, BMC D12, 221 84, Lund, Sweden. bengt-olof.nilsson@med.lu.se.
authors.forename: Bengt-Olof
authors.identifier: http://orcid.org/0000-0003-2337-8412
authors.initials: BO
authors.lastname: Nilsson
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics*; D002762:Cholecalciferol / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis*; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D014808:Vitamin D Deficiency / Q000378:metabolism; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; D002762:Cholecalciferol; D054804:Cathelicidins
keywords: Chemokine; Cytokine; Innate immune system; Vitamin D3; hCAP-18/LL-37