Pini A., Somma T., Formicola G., Lucarini L., Bani D., Thurmond R. and Masini E. Pages 1338 - 1344 ( 7 )
The histamine H<sub>4</sub> receptor (H<sub>4</sub>R), 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 H<sub>4</sub>R antagonists can decrease airway inflammation and hyperreactivity in animal models of asthma. </p> <p> In the present study we evaluated the effect of the selective H<sub>4</sub>R antagonist JNJ7777120 (JNJ) in carrageenan-induced pleurisy, an in vivo model of inflammation, well characterized for cellular and molecular mechanisms. </p> <p> 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, PgE<sub>2</sub> and 6-ketoPgF<sub>1α</sub>, 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. </p> <p> The pre-treatment with JNJ (5-10 mg Kg<sup>-1</sup> b.wt., given intrapleurally), 60 min before carrageenan markedly reduced all the studied parameters. This study clearly demonstrated that histamine H<sub>4</sub>R antagonists have anti-inflammatory effects and could have potential therapeutic application for the treatment of inflammatory diseases.
Apoptosis, carrageenan, cytokines, inflammation pleurisy, JNJ7777120.
, , , , , , Department of NEUROFARBA, Sect. of Pharmacology, University of Florence, Viale G. Pieraccini n.6, 50139 Florence (Italy).