Histamine down-regulates IL-27 production in antigen-presenting cells

J Leukoc Biol. 2012 Jul;92(1):21-9. doi: 10.1189/jlb.0111017. Epub 2012 Mar 2.

Abstract

Histamine is a potent mediator in allergic inflammation with immunomodulatory properties. Since histamine was described to inhibit IL-12 production in human APCs, we hypothesized that also the expression of IL-27, a newly described member of the IL-12 family, which is present in inflammatory skin lesions, is modulated by histamine. Stimulation of human monocytes with histamine resulted in significant reduction of TLR ligand-induced IL-27 production in human monocytes. IL-27 subunits, p28 and EBI3, were down-regulated at the mRNA and protein level, whereas other cytokines, such as IL-6, IL-10, and TNF-α, were not influenced. Studies with histamine receptor-specific agonists and antagonists showed that the down-regulation of IL-27 was mediated via H(2)R and H(4)R but not H(1)R and H(3)R. Human KCs treated with supernatants of histamine-prestimulated monocytes induced significantly less CXCL10 than supernatants containing high levels of IL-27. DCs from H(4)R(-/-) mice responded to TLR simulation with higher IL-27 production as compared with WT mice. The down-regulation of IL-27 by histamine might be a new mechanism in the pathogenesis of inflammatory skin diseases, in particular, if increased concentrations of histamine are present at sites of inflammation, such as in chronic eczema and psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / drug effects*
  • Antigen-Presenting Cells / metabolism*
  • Blotting, Western
  • Cells, Cultured
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism
  • Down-Regulation
  • Enzyme-Linked Immunosorbent Assay
  • Histamine / pharmacology*
  • Histamine Agonists / pharmacology*
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-12 / genetics
  • Interleukin-12 / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / metabolism
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Receptors, Histamine / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Histamine Agonists
  • Il27 protein, mouse
  • Interleukin-6
  • Interleukins
  • MYDGF protein, human
  • RNA, Messenger
  • Receptors, Histamine
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12
  • Histamine
  • Interferon-gamma