Meteorin-like/Meteorin-β upregulates proinflammatory cytokines via NF-κB pathway in grass carp Ctenopharyngodon idella

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 CiMetrnl-a and CiMetrnl-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 CiMetrnl-a gene was constitutively expressed in tissues of healthy fish whilst the levels of CiMetrnl-b transcripts were too low to be detected. The CiMetrnl-a gene was inducible by Flavobacterium columnare, grass carp reovirus and PAMPs. Recombinant CiMetrnl-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 CiMetrnl-a was able to activate the NF-κB promoter in the EPC cells, suggesting that CiMetrnl-a may upregulate pro-inflammatory cytokines via NF-κB dependent pathway.