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Histamine down-regulates IL-27 production in antigen-presenting cells
Maria Gschwandtner1, Hannah Bunk, Brigitta Köther
1Hannover Medical School, Department of Dermatology and Allergy, Division of Immunodermatology and Allergy Research, Hannover, Germany. maria_gschwandtner@gmx
Journal of Leukocyte Biology
|March 6, 2012
Summary
Histamine reduces the production of Interleukin-27 (IL-27), a key cytokine in immune responses, particularly in inflammatory skin conditions. This histamine-induced down-regulation may play a role in diseases like eczema and psoriasis.
Area of Science:
- Immunology
- Dermatology
- Molecular Biology
Background:
- Histamine is a key mediator in allergic inflammation.
- Histamine is known to inhibit Interleukin-12 (IL-12) production in human antigen-presenting cells (APCs).
- Interleukin-27 (IL-27), a member of the IL-12 family, is found in inflammatory skin lesions.
Purpose of the Study:
- To investigate whether histamine modulates the expression of IL-27.
- To explore the role of histamine in the regulation of IL-27 production in human monocytes.
- To understand the potential implications of histamine's effect on IL-27 in inflammatory skin diseases.
Main Methods:
- Human monocytes were stimulated with histamine and Toll-like receptor (TLR) ligands.
- Quantitative real-time PCR and Western blotting were used to assess mRNA and protein levels of IL-27 subunits (p28 and EBI3).
- Histamine receptor agonists and antagonists were employed to identify mediating receptors; experiments with H(4)R(-/-) mice and human keratinocytes (KCs) were also conducted.
Main Results:
- Histamine stimulation significantly reduced TLR ligand-induced IL-27 production in human monocytes.
- Down-regulation of IL-27 subunits (p28 and EBI3) occurred at both mRNA and protein levels.
- The effect was mediated via histamine receptors H(2)R and H(4)R, with no involvement of H(1)R or H(3)R. H(4)R(-/-) mice showed increased IL-27 production. Histamine-pretreated monocyte supernatants reduced CXCL10 production in KCs.
Conclusions:
- Histamine down-regulates IL-27 production in human monocytes through H(2)R and H(4)R.
- This histamine-mediated reduction of IL-27 may represent a novel mechanism in the pathogenesis of inflammatory skin diseases.
- The findings are particularly relevant for conditions with elevated histamine levels, such as chronic eczema and psoriasis.
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