jnj-7777120 and Psoriasis

Previous studies have shown the expression of histamine H. This study aimed to investigate the role of H4R on these effector T cells in psoriasis.. We enrolled three patients each with active psoriasis, inactive psoriasis, scalp seborrheic dermatitis, and three normal controls, and compared the basal expression of H4R mRNA in their peripheral blood CD4. The results showed higher H4R expression in the active psoriasis group compared to the inactive psoriasis group. It was interesting that interleukin (IL)-23, which is a representative cytokine contributing to T. Histamine stimulation influences the IL-17 pathway in psoriasis via the fourth histamine receptor subtype, H4R, on CD4

Topics: Cell Separation; Dermatitis, Seborrheic; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Histamine; Humans; Indoles; Interleukin-17; Interleukin-23; Piperazines; Psoriasis; Receptors, Histamine H4; Recombinant Proteins; Signal Transduction; Th17 Cells

6-Sulpho LacNAc dendritic cells (slanDC) are a major population of human blood DC that are highly pro-inflammatory, as characterized by their outstanding capacity to produce tumour necrosis factor-α and interleukin-12 (IL-12) and to prime antigen-specific T-cell responses. SlanDC were found to be present in inflamed tissue such as atopic dermatitis, where high levels of histamine are also present. As histamine is an important regulator of allergic inflammation we investigated the role of histamine receptors, particularly the most recently identified histamine H(4) receptor (H(4) R), in modulating the pro-inflammatory function of slanDC. The expression of H(4) R was evaluated by real-time PCR and flow cytometry. Cytokine production in response to H(4) R stimulation was assessed by intracellular flow cytometric staining and enzyme-linked immunosorbent assay. We show that slanDC express the H(1) R, H(2) R and H(4) R on mRNA and the H(4) R on protein level. No differences were observed in basal H(4) R expression in patients with atopic dermatitis and psoriasis, but in atopic dermatitis patients the H(4) R was up-regulated by interferon-γ. When stimulated with lipopolysaccharide in the presence of histamine, slanDC produced substantially lower levels of the pro-inflammatory cytokines tumour necrosis factor-α and IL-12, mediated solely via the H(4) R and via the combined action of H(2) R and H(4) R, respectively. In contrast, the production of IL-10 was not affected by histamine receptor activation on slanDC. The slanDC express the H(4) R and its stimulation leads to reduced pro-inflammatory capacity of slanDC. Hence, H(4) R agonists might have therapeutic potential to down-regulate immune reactions, e.g. in allergic inflammatory skin diseases.

Topics: Amino Sugars; Cytokines; Dendritic Cells; Dermatitis, Atopic; Flow Cytometry; Histamine; Humans; Indoles; Inflammation; Interferon-gamma; Lipopolysaccharides; Methylhistamines; Piperazines; Psoriasis; Receptors, G-Protein-Coupled; Receptors, Histamine; Receptors, Histamine H4; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger