The histamine H(4) receptor: a novel modulator of inflammatory and immune disorders.
All 4 known histamine receptors (H(1)R, H(2)R, H(3)R and H(4)R) have been used or proposed as therapeutic targets for varied diseases. This article reviews the recent progress in understanding the function of the recently described histamine receptor H(4)R in a variety of immune responses and the potential therapeutic value of H(4)R antagonists. The H(4)R is expressed primarily on cells involved in inflammation and immune response. It has effects on chemotaxis, as well as cytokine and chemokine production of mast cells, eosinophils, dendritic cells, and T cells. H(4)R antagonists, JNJ 7777120 and JNJ 10191584 (also known as VUF 6002) have been developed with excellent affinity and selectivity towards human and rodent H(4)R. These antagonists also demonstrate efficacy as anti-inflammatory agents in vivo. H(4)R antagonists have shown promising activity in down-regulating immune responses in a range of animal disease models including acute inflammation, hapten-mediated colitis, and allergic airway inflammation. Due to its distribution on immune cells and its proven role in inflammatory functions, the H(4)R appears to be a therapeutic target for the treatment of a variety of immune disorders.
Zhang
Mai
M
Johnson & Johnson Pharmaceutical Research and Development L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA.
Thurmond
Robin L
RL
Dunford
Paul J
PJ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000493:pharmacokinetics / Q000494:pharmacology; D002633:Chemotaxis / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects; D016503:Drug Delivery Systems; D005786:Gene Expression Regulation; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy*; D007211:Indoles / Q000493:pharmacokinetics / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy*; D010879:Piperazines / Q000493:pharmacokinetics / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D011968:Receptors, Histamine / Q000187:drug effects / Q000502:physiology*; D000074040:Receptors, Histamine H4
D000893:Anti-Inflammatory Agents; D001562:Benzimidazoles; D016207:Cytokines; C418607:HRH4 protein, human; D007211:Indoles; C506811:JNJ 10191584; D010879:Piperazines; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; C484309:1-((5-chloro-1H-indol-2-yl)carbonyl)-4-methylpiperazine