My NCBI | Sign In
RSS Settings
  • Search:

Display Settings:

Format

Send to:

Choose Destination

    Proc Natl Acad Sci U S A. 2006 May 16;103(20):7777-82. Epub 2006 May 8.

    Simvastatin promotes Th2-type responses through the induction of the chitinase family member Ym1 in dendritic cells.

    Arora M, Chen L, Paglia M, Gallagher I, Allen JE, Vyas YM, Ray A, Ray P.

    Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.

    Statins, best known for their lipid-lowering actions, also possess immunomodulatory properties. Recent studies have shown a Th2-biasing effect of statins, although the underlying mechanism has not been identified. In this study, we investigated whether simvastatin can exercise a Th2-promoting effect through modulation of function of dendritic cells (DCs) without direct interaction with CD4+ T cells. Exposure of DCs to simvastatin induced the differentiation of a distinct subset of DCs characterized by a high expression of B220. These simvastatin-conditioned DCs up-regulated GATA-3 expression and down-regulated T-bet expression in cocultured CD4+ T cells in the absence of additional simvastatin added to the coculture. The Th2-biased transcription factor profile induced by simvastatin-treated DCs also was accompanied by increased Th2 (IL-4, IL-5, and IL-13) and decreased Th1 (IFN-gamma) cytokine secretion from the T cells. The Th2-promoting effect of simvastatin was found to depend on the chitinase family member Ym1, known to be a lectin. Anti-Ym1 antibody abolished the Th2-promoting effect of simvastatin-treated DCs. Also, simvastatin was unable to augment Ym1 expression in DCs developed from STAT6-/- or IL-4R alpha-/- mice. Thus, modulation of Ym1 production by DCs identifies a previously undescribed mechanism of Th2 polarization by statin.

    PMID: 16682645 [PubMed - indexed for MEDLINE]

    PMCID: 1472521

    Publication Types, MeSH Terms, Substances, Grant Support

    Publication Types:

    MeSH Terms:

    Substances:

    Grant Support:

    LinkOut - more resources

    Full Text Sources:

    Other Literature Sources:

    Libraries:

    Supplemental Content

    Click here to read Click here to read Click here to read Click here to read

    Related articles

    Cited by 5 PubMed Central articles

    Patient drug information

    All links from this record

    • Related Articles

      Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.

    • Compound (MeSH Keyword)

      PubChem chemical compound records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.

    • Gene

      Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.

    • Gene (GeneRIF)

      Gene records that have the current articles as Reference into Function citations (GeneRIFs). NLM staff reviewing the literature while indexing MEDLINE add GeneRIFs manually.

    • HomoloGene

      HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.

    • Nucleotide (RefSeq)

      NCBI nucleotide Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.

    • Nucleotide (Weighted)

      Nucleotide records associated with the current articles through the Gene database. These are the related sequences on the Gene record that are added manually by NCBI.

    • Protein (RefSeq)

      NCBI protein Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.

    • Protein (Weighted)

      Protein records associated with the current articles through related Gene database records. These are the related sequences on the Gene record that are added manually by NCBI.

    • References for this PMC Article

      Citation referenced in PubMed article. Only valid for PubMed citations that are also in PMC.

    • Substance (MeSH Keyword)

      PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.

    • Taxonomy via GenBank

      Taxonomy records associated with the current articles through taxonomic information on related molecular database records (Nucleotide, Protein, Gene, SNP, Structure).

    • UniGene

      UniGene clusters of expressed sequences that are associated with the current articles through references on the clustered sequence records and related Gene records.

    • GEO Profiles

      Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.

    • Free in PMC

      Free full text articles in PMC

    • Cited in PMC

      Full-text articles in the PubMed Central Database that cite the current articles.

    Recent activity