title: Assessment of CCL2 and CXCL8 chemokines in serum, bronchoalveolar lavage fluid and lung tissue samples from dogs affected with canine idiopathic pulmonary fibrosis.
abstract: Canine idiopathic pulmonary fibrosis (CIPF) is a progressive disease of the lung parenchyma that is more prevalent in dogs of the West Highland white terrier (WHWT) breed. Since the chemokines (C-C motif) ligand 2 (CCL2) and (C-X-C motif) ligand 8 (CXCL8) have been implicated in pulmonary fibrosis in humans, the aim of the present study was to investigate whether these same chemokines are involved in the pathogenesis of CIPF. CCL2 and CXCL8 concentrations were measured by ELISA in serum and bronchoalveolar lavage fluid (BALF) from healthy dogs and WHWTs affected with CIPF. Expression of the genes encoding CCL2 and CXCL8 and their respective receptors, namely (C-C motif) receptor 2 (CCR2) and (C-X-C motif) receptor 2 (CXCR2), was compared in unaffected lung tissue and biopsies from dogs affected with CIPF by quantitative PCR and localisation of CCL2 and CXCL8 proteins were determined by immunohistochemistry. Significantly greater CCL2 and CXCL8 concentrations were found in the BALF from WHWTs affected with CIPF, compared with healthy dogs. Significantly greater serum concentrations of CCL2, but not CXCL8, were found in CIPF-affected dogs compared with healthy WHWTs. No differences in relative gene expression for CCL2, CXCL8, CCR2 or CXCR2 were observed when comparing lung biopsies from control dogs and those affected with CIPF. In affected lung tissues, immunolabelling for CCL2 and CXCL8 was observed in bronchial airway epithelial cells in dogs affected with CIPF. The study findings suggest that both CCL2 and CXCL8 are involved in the pathogenesis of CIPF. Further studies are required to determine whether these chemokines might have a clinical use as biomarkers of fibrosis or as targets for therapeutic intervention.
authors.affiliation: Faculty of Veterinary Medicine, University of Liège, Bd de Colonster, Liège, Belgium. Electronic address: eroels@ulg.ac.be.
authors.forename: Elodie
authors.initials: E
authors.lastname: Roels
authors.affiliation: Faculty of Veterinary Medicine, University of Liège, Bd de Colonster, Liège, Belgium.
authors.forename: Emilie
authors.initials: E
authors.lastname: Krafft
authors.affiliation: Faculty of Veterinary Medicine, University of Liège, Bd de Colonster, Liège, Belgium.
authors.forename: Frederic
authors.initials: F
authors.lastname: Farnir
authors.affiliation: Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, PO Box 57, 00014 Helsinki, Finland.
authors.forename: Saila
authors.initials: S
authors.lastname: Holopainen
authors.affiliation: Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, PO Box 57, 00014 Helsinki, Finland.
authors.forename: Henna P
authors.initials: HP
authors.lastname: Laurila
authors.affiliation: Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, PO Box 57, 00014 Helsinki, Finland.
authors.forename: Minna M
authors.initials: MM
authors.lastname: Rajamäki
authors.affiliation: School of Veterinary Sciences, University of Bristol, Langford BS40 5DU, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Day
authors.affiliation: Faculty of Veterinary Medicine, University of Liège, Bd de Colonster, Liège, Belgium.
authors.forename: Nadine
authors.initials: N
authors.lastname: Antoine
authors.affiliation: Department of Functional Sciences, Cellular and Molecular Immunology, GIGA-Research, University of Liège, Av de l'Hôpital, Liège, Belgium.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Pirottin
authors.affiliation: Faculty of Veterinary Medicine, University of Liège, Bd de Colonster, Liège, Belgium.
authors.forename: Cecile
authors.initials: C
authors.lastname: Clercx
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D018932:Chemokine CCL2 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D004283:Dog Diseases / Q000378:metabolism*; D004285:Dogs; D005260:Female; D054990:Idiopathic Pulmonary Fibrosis / Q000097:blood / Q000378:metabolism / Q000662:veterinary*; D016209:Interleukin-8 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male
chemical_list: D018932:Chemokine CCL2; D016209:Interleukin-8
keywords: CCL2; CXCL8; Canine idiopathic pulmonary fibrosis; Chemokine