Inhibitory effect of a histamine 4 receptor antagonist on CCL17 and CCL22 production by monocyte-derived Langerhans cells in patients with atopic dermatitis.

Abstract

We examined the inhibitory effect of a histamine 4 receptor (H4R) antagonist (JNJ7777120) on CCL17 and CCL22 chemokine production by human monocyte-derived Langerhans cells (MoLC) in patients with atopic dermatitis (AD) and healthy controls (HC). We confirmed the significantly higher production of both CCL17 and CCL22 in the MoLC of AD patients compared with HC. The H4R antagonist significantly inhibited the production of both CCL17 and CCL22 in the MoLC of AD patients. With regard to TLR2-signaled enhancement, peptidoglycan (PGN)-enhanced production of CCL17 and CCL22 by MoLC was inhibited by the H4R. Immunoblotting analysis demonstrated that phosphorylated p38 mitogen-activated protein kinase was induced by PGN and that this enhancement was attenuated by the application of the H4R antagonist. These data indicate that H4 signaling modulates the production of T-helper 2 chemokine in MoLC and contributes to chronic inflammation in AD patients. Our data suggest a possible novel therapeutic approach using a H4R antagonist in the treatment of patients with AD.

• Authors: Kyohei Miyano, Sho Matsushita, Tetsuya Tsuchida, Koichiro Nakamura
• Journal: The Journal of dermatology (J Dermatol) Vol. 43 Issue 9 Pg. 1024-9 (Sep 2016) ISSN: 1346-8138 [Electronic] England
• PMID: 26892271 (Publication Type: Journal Article)
• Copyright: © 2016 Japanese Dermatological Association.

Chemical References

• CCL17 protein, human
• CCL22 protein, human
• Chemokine CCL17
• Chemokine CCL22
• HRH4 protein, human
• Indoles
• Peptidoglycan
• Piperazines
• Receptors, G-Protein-Coupled
• Receptors, Histamine
• Receptors, Histamine H4
• TLR2 protein, human
• Toll-Like Receptor 2
• 1-((5-chloro-1H-indol-2-yl)carbonyl)-4-methylpiperazine
• p38 Mitogen-Activated Protein Kinases

Topics

• Cells, Cultured
• Chemokine CCL17 (metabolism)
• Chemokine CCL22 (metabolism)
• Dermatitis, Atopic (metabolism)
• Humans
• Indoles (pharmacology, therapeutic use)
• Langerhans Cells (drug effects, metabolism)
• Monocytes (cytology)
• Peptidoglycan (metabolism)
• Piperazines (pharmacology, therapeutic use)
• Receptors, G-Protein-Coupled (antagonists & inhibitors)
• Receptors, Histamine
• Receptors, Histamine H4
• Signal Transduction
• Staphylococcus aureus (metabolism)
• Th2 Cells (metabolism)
• Toll-Like Receptor 2 (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)