Expression and function of human hemokinin-1 in human and guinea pig airways

<p>Abstract</p> <p>Background</p> <p>Human hemokinin-1 (hHK-1) and endokinins are peptides of the tachykinin family encoded by the <it>TAC4 </it>gene. <it>TAC4 </it>and hHK-1 expression as well as effects of hHK-1 in the lung and airways remain however unknown and were explored in this study.</p> <p>Methods</p> <p>RT-PCR analysis was performed on human bronchi to assess expression of tachykinin and tachykinin receptors genes. Enzyme immunoassay was used to quantify hHK-1, and effects of hHK-1 and endokinins on contraction of human and guinea pig airways were then evaluated, as well as the role of hHK-1 on cytokines production by human lung parenchyma or bronchi explants and by lung macrophages.</p> <p>Results</p> <p>In human bronchi, expression of the genes that encode for hHK-1, tachykinin NK₁-and NK₂-receptors was demonstrated. hHK-1 protein was found in supernatants from explants of human bronchi, lung parenchyma and lung macrophages. Exogenous hHK-1 caused a contractile response in human bronchi mainly through the activation of NK₂-receptors, which blockade unmasked a NK₁-receptor involvement, subject to a rapid desensitization. In the guinea pig trachea, hHK-1 caused a concentration-dependant contraction mainly mediated through the activation of NK₁-receptors. Endokinin A/B exerted similar effects to hHK-1 on both human bronchi and guinea pig trachea, whereas endokinins C and D were inactive. hHK-1 had no impact on the production of cytokines by explants of human bronchi or lung parenchyma, or by human lung macrophages.</p> <p>Conclusions</p> <p>We demonstrate endogenous expression of <it>TAC4 </it>in human bronchi, the encoded peptide hHK-1 being expressed and involved in contraction of human and guinea pig airways.</p