Neurotensin alleviates airway inflammation in murine model of hapten-induced asthma

Abstract

Neurotensin (NTS) is an oligopeptide, which shows ambiguous activity in inflammatory process. The aim of the study was to test potential anti-inflammatory activity of NTS in mice model of non-atopic asthma and establish the contribution of NTS1 receptors. Asthma was induced in BALB/c mice by skin sensitization with dinitrofluorobenzene followed by intratracheal challenge of dinitrobenzene sulfonic acid. After hapten provocation and 8 hr later, mice were treated intraperitoneally with NTS, SR142948 (NTS1 receptor antagonist)+NTS or NaCl. 24 hr after challenge airway responsiveness to nebulized methacholine was measured in plethysmographic chamber. Bronchoalveolar lavage fluid (BALF) and differential cell count was performed. BALF and lung homogenates were used to quantify the levels of cytokines, mouse mast cell protease (mMCP-1) and malondialdehyde (MDA). NTS alleviated bronchial hyperreactivity and reduced number of inflammatory cells in BALF. Administration of NTS1 receptor antagonist inhibited these beneficial effects. Treatment with neurotensin decreased levels of IL-13, TNF-a in BALF and IL-17A, IL-12p40, RANTES, mMCP-1, MDA in lung tissue homogenates. SR142948 blockade reverted only post-neurotensin TNF-a decrease. NTS exhibits anti-inflammatory activity in hapten-induced asthma model. Leukocyte accumulation and bronchial constriction studies indicate, that this beneficial NTS action is mediated through NTS1 receptors. No effect of NTS1 blockade on mast cells activation product, oxidative stress marker and pro-inflammatory cytokine production suggest that NTS2 receptor can be involved. Further research is required. Financial support: National Science Centre, Poland, 2014/13/B/NZ7/02247