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

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.

• Authors: Maria Gschwandtner, Hannah Bunk, Brigitta Köther, Robin L Thurmond, Manfred Kietzmann, Thomas Werfel, Wolfgang Bäumer, Ralf Gutzmer
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 92 Issue 1 Pg. 21-9 (Jul 2012) ISSN: 1938-3673 [Electronic] United States
• PMID: 22389321 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

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