A selective antagonist of histamine H4 receptors prevents antigen‐induced airway inflammation and bronchoconstriction in guinea pigs: involvement of lipocortin‐1. (15th August 2013)

• Record Type: Journal Article
• Authors: Somma, T; Cinci, L; Formicola, G; Pini, A; Thurmond, R; Ennis, M; Bani, D; Masini, E
• Is Part Of: British journal of pharmacology. Volume 170:Number 1(2013:Sep.)
• Page Start: 200
• Page End: 213
• Publication Date: 2013-08-15
• Subjects: Pharmacology -- Periodicals; Chemotherapy -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/bph.12264
• Languages: English
• ISSNs: 0007-1188

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bph12264-sec-0001" sec-type="section"> <title>Background and Purpose</title> <p>Among the pathogenic mechanisms of asthma, a role for oxidative/nitrosative stress has been well documented. Recent evidence suggests that histamine H<sub>4</sub> receptors play a modulatory role in allergic inflammation. Here we report the effects of compound JNJ 7777120 (JNJ), a selective H<sub>4</sub> receptor antagonist, on antigen‐induced airway inflammation, paying special attention to its effects on lipocortin‐1 (LC‐1/annexin‐A1), a 37 kDA anti‐inflammatory protein that plays a key role in the production of inflammatory mediators.</p> </sec> <sec id="bph12264-sec-0002" sec-type="section"> <title>Experimental Approach</title> <p>Ovalbumin (OA)‐sensitized guinea pigs placed in a respiratory chamber were challenged with antigen. JNJ (5, 7.5 and 10 mg·kg<sup>−1</sup>) was given i.p. for 4 days before antigen challenge. Respiratory parameters were recorded. Bronchoalveolar lavage (BAL) fluid was collected and lung specimens taken for further analyses 1 h after antigen challenge. In BAL fluid, levels of LC‐1, PGD<sub>2</sub>, LTB<sub>4</sub> and TNF‐α were measured. In lung tissue samples, myeloperoxidase, caspase‐3 and Mn‐superoxide dismutase activities and 8‐hydroxy‐2‐deoxyguanosine levels were measured.</p> </sec> <sec id="bph12264-sec-0003" sec-type="section"> <title>Key Results</title> <p>OA challenge decreased LC‐1 levels in BAL fluid, induced cough, dyspnoea and bronchoconstriction and increased PGD<sub>2</sub>, LTB<sub>4</sub> and TNF‐α levels in lung tissue. Treatment with JNJ dose‐dependently increased levels of LC‐1, reduced respiratory abnormalities and lowered levels of PGD<sub>2</sub>, LTB<sub>4</sub> and TNF‐α in BAL fluid.</p> </sec> <sec id="bph12264-sec-0004" sec-type="section"> <title>Conclusions and Implications</title> <p>Antigen‐induced asthma‐like reactions in guinea pigs decreased levels of LC‐1 and increased TNF‐α and eicosanoid production. JNJ pretreatment reduced allergic asthmatic responses and airway inflammation, an effect associated with LC‐1 up‐regulation.</p> </sec> <sec id="bph12264-sec-5001" sec-type="relatedArticles"> <title>Linked Articles</title> <p>This article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2013.170.issue‐1</p> </sec> </abstract>