title: Effects of a selective histamine H₄R antagonist on inflammation in a model of carrageenan-induced pleurisy in the rat.
abstract: The histamine H₄ receptor (H₄R), recently cloned and identified, is a G-protein coupled histamine receptor family expressed in immune cells which plays an important role in inflammation. Recent data evidentiated that H₄R antagonists can decrease airway inflammation and hyperreactivity in animal models of asthma. In the present study we evaluated the effect of the selective H₄R antagonist JNJ7777120 (JNJ) in carrageenan-induced pleurisy, an in vivo model of inflammation, well characterized for cellular and molecular mechanisms. Intra-pleural administration of λ-carrageenan (1% w/v in 0.2 ml sterile saline) determined an intense recruitment of leucocytes in pleural exudates and in lung tissues, activated inducible nitric oxide (NO) synthase and cyclooxygenase-2, thus increasing the generation of harmful autacoids such as NO and pro-inflammatory prostaglandins, PgE₂ and 6-ketoPgF(1α), increased cellular and DNA oxidative stress, measured as malondialdehyde and 8-OH-deoxyguanosine and the local generation of IL-1β and TNF-α. Moreover, the activity of caspase-3, an early marker of apoptosis was also activated by λ-carrageenan injection. The pre-treatment with JNJ (5-10 mg Kg⁻¹ b.wt., given intrapleurally), 60 min before carrageenan markedly reduced all the studied parameters. This study clearly demonstrated that histamine H₄R antagonists have anti-inflammatory effects and could have potential therapeutic application for the treatment of inflammatory diseases.
authors: A
authors: A
authors: Pini
authors: T
authors: T
authors: Somma
authors: G
authors: G
authors: Formicola
authors: L
authors: L
authors: Lucarini
authors: D
authors: D
authors: Bani
authors: R
authors: R
authors: Thurmond
authors: Department of NEUROFARBA, Sect. of Pharmacology, University of Florence, Viale G. Pieraccini n.6, 50139 Florence (Italy). emanuela.masini@unifi.it.
authors: E
authors: E
authors: Masini
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002351:Carrageenan / Q000633:toxicity; D053148:Caspase 3 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D006633:Histamine Antagonists / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D010998:Pleurisy / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4
chemical_list: D000893:Anti-Inflammatory Agents; D006633:Histamine Antagonists; C498828:Hrh4 protein, rat; D007211:Indoles; 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; D002351:Carrageenan; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D053148:Caspase 3