Abstract

Meteorin-like (Metrnl) is a newly discovered cytokine but whether it exists in fish is unclear. In this study, we identified two Meteorin-like (Metrnl) homologues in grass carp Ctenopharyngodon idella (termed Ci Metrnl-a and Ci Metrnl-b) which share high sequence homology and conserved genomic organization of 4 exons and 3 introns with known Metrnl molecules. Also, gene synteny of Metrnl genes is well conserved in vertebrates. Expression analyses showed that the Ci Metrnl-a gene was constitutively expressed in tissues of healthy fish whilst the levels of Ci Metrnl-b transcripts were too low to be detected. The Ci Metrnl-a gene was inducible by Flavobacterium columnare, grass carp reovirus and PAMPs . Recombinant Ci Metrnl-a produced in the CHO-S cells was active in up-regulating the expression of cytokines involved in promoting inflammation (IL-1β, IL-6, IL-8, IL-17A and TNF-α), type 1 immune response (IFN-γ and IL-2) and NF-κB signaling pathway (NF-κBp65 and NF-κBp52) in the primary head kidney leukocytes. Furthermore, luciferase reporter assay showed that Ci Metrnl-a was able to activate the NF-κB promoter in the EPC cells, suggesting that Ci Metrnl-a may upregulate pro-inflammatory cytokines via NF-κB dependent pathway.