Human inflammatory dendritic epidermal cells express a functional histamine H4 receptor.
Expression of histamine H(4) receptor (H(4)R) on leukocytes suggests an immunomodulatory role of this receptor. Here we investigated the expression and function of H(4)R on human inflammatory dendritic epidermal cells (IDECs). H(4)R is expressed by IDEC of the skin. On monocyte-derived IDECs (Mo-IDECs), H(4)R is also expressed and upregulated by IFN-gamma. Functionally, histamine and H(4)R agonists clobenpropit and 4-methylhistamine downregulated the production of the Th2-linked chemokine CCL2 and the Th1 cytokine IL-12 on Mo-IDEC, whereas agonists for the other histamine receptors did not. An H(4)R-selective antagonist (JNJ7777120) blocked the effect of H(4)R agonists. Downregulation of CCL2 also led to a decreased migration of monocytes. Thus, IDEC express a functionally active H(4)R, which upon stimulation leads to downregulation of CCL2 and IL-12. This might have implications for the treatment of atopic dermatitis, since H(4)R agonists may have beneficial effects in downregulating inflammation.
Dijkstra
Dorothea
D
Department of Dermatology and Allergology, Hannover Medical School, Hannover, Germany. dijkstra.dorothea@mh-hannover.de
Stark
Holger
H
Chazot
Paul L
PL
Shenton
Fiona C
FC
Leurs
Rob
R
Werfel
Thomas
T
Gutzmer
Ralf
R
D018955:CD36 Antigens / Q000032:analysis; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D002634:Chemotaxis, Leukocyte; D003713:Dendritic Cells / Q000276:immunology*; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000032:analysis; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000032:analysis; D009000:Monocytes / Q000276:immunology; D011956:Receptors, Cell Surface / Q000032:analysis; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000032:analysis / Q000502:physiology*; D011968:Receptors, Histamine / Q000032:analysis / Q000502:physiology*; D000074040:Receptors, Histamine H4; D012867:Skin / Q000276:immunology*
C111835:CCL2 protein, human; D018955:CD36 Antigens; D018932:Chemokine CCL2; C418607:HRH4 protein, human; D053762:Interleukin-12 Subunit p40; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4