Human Molecular Genetics Advance Access published online on April 6, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl090
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1 Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
* To whom correspondence should be addressed. G protein-coupled receptor 154 (GPR154) is a recently discovered asthma susceptibility gene upregulated in the airways of asthma patients. We previously observed increased pulmonary mRNA expression of the murine ortholog Gpr154 in a mouse model of ovalbumin-induced inflammation. However, the expression profile of GPR154 in leukocytes and the cellular functions of the receptor and its endogenous agonist Neuropeptide S (NPS) have remained unidentified. Here, we characterised the mRNA expression of NPS and GPR154 by using real-time RT-PCR in fractioned human blood cells and in peripheral blood mononuclear cells (PBMCs) with monocyte or T cell activation. The expression of GPR154 in leukocytes was further confirmed by immunoblotting experiments and immunohistochemical staining of human sputum samples. Additionally, we characterised the expression of GPR154 in the lung tissue samples and in the bronchoalveolar lavage (BAL) fluid of ovalbumin sensitized and challenged BALB/c mice. In human blood and sputum cells, monocyte/macrophages and eosinophils were identified as GPR154-positive cells. In PBMCs, monocyte activation with LPS but not T cell activation with anti-CD3/CD28 antibodies resulted in increased NPS and GPR154 expression. In the lung tissue samples and in the BAL fluid of ovalbumin-challenged mice, GPR154 expression was upregulated in alveolar macrophages in comparison to controls. In the mouse macrophage RAW 264.7 cell line, NPS stimulated G
Received January 25, 2006
Revised March 29, 2006
Accepted March 29, 2006
Article
Neuropeptide S and G protein-coupled receptor 154 modulate macrophage immune responses
Ville Pulkkinen 1,
Marja-Leena Majuri 2,
Guoying Wang 2,
Päivi Holopainen 3,
Yasushi Obase 4,
Johanna Vendelin 1,
Henrik Wolff 5,
Paula Rytilä 4,
Lauri A. Laitinen 6,
Tari Haahtela 4,
Tarja Laitinen 7,
Harri Alenius 2,
Juha Kere 8 *,
and
Marko Rehn 9
2 Finnish Institute of Occupational Health, Helsinki, Finland
3 Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Swiss Institute of Allergy and Asthma Research, Davos, Switzerland
4 Department of Allergy, Helsinki University Central Hospital Helsinki, Finland
5 Finnish Institute of Occupational Health, Helsinki, Finland; Department of pathology, University of Helsinki, Finland
6 Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
7 Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; GeneOS Ltd, Helsinki, Finland
8 Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Department of Biosciences and Nutrition at Novum and Clinical research centre, Karolinska Institutet, Huddinge, Sweden
9 GeneOS Ltd, Helsinki, Finland
Juha Kere, E-mail: juha.kere{at}biosci.ki.se
Abstract 
s and Gq -dependent phagocytosis of E. coli. The results show that GPR154 is upregulated in macrophages after antigen challenge and that NPS is capable of inducing phagocytosis of unopsonised bacteria.
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