Effects Of A Selective Histamine H4R Antagonist On Inflammation In A Model Of Carrageenan-Induced Pleurisy In The Rat
Pini A., Somma T., Formicola G., Lucarini L., Bani D., Thurmond R. and Masini E.
Affiliation: Department of NEUROFARBA, Sect. of Pharmacology, University of Florence, Viale G. Pieraccini n.6, 50139 Florence (Italy).
Keywords: Apoptosis, carrageenan, cytokines, inflammation pleurisy, JNJ7777120.
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-ketoPgF1α, 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.
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