PMID- 34228995 OWN - NLM STAT- MEDLINE DCOM- 20220324 LR - 20220324 IS - 1879-0089 (Electronic) IS - 0145-305X (Linking) VI - 124 DP - 2021 Nov TI - Characterization of the turbot (Scophthalmus maximus) interleukin-18: Identification of splicing variants, phylogeny, synteny and expression analysis. PG - 104199 LID - S0145-305X(21)00207-X [pii] LID - 10.1016/j.dci.2021.104199 [doi] AB - Interleukin-18 (IL-18) is a pro-inflammatory cytokine that belongs to the interleukin-1 (IL-1) family of cytokines. As occurs with IL-1beta, it is synthetized as an inactive precursor peptide that is mainly processed by the cysteine protease caspase-1 in the inflammasome complex. In mammals, and in collaboration with IL-12, it has been described as an important cytokine controlling the Th1-mediated immune responses through the induction of IFN-gamma. Although its function in mammals is well stablished, the activity of this cytokine in teleost remains to be elucidated. This could be due, among other things, to the absence of this gene in the fish model species zebrafish, but also to its complex regulation. As it was observed for rainbow trout and human, il18 splicing variants were also found in turbot, which could represent a regulatory mechanism of its bioactivity. In the case of turbot, three splicing variants were observed (SV1-3), and one of them showed an insertion of 10 amino acids in the middle of the potential caspase-1 cleavage position, reflecting that this is probably a form resistant to the processing by the inflammasome. Phylogenetic and three-dimensional analyses of turbot Il18 revealed that it is relatively well-conserved in vertebrates, although only a partial conservation of the gene synteny was observed between fish and mammals. As it was expected, turbot il18 splicing variants were mainly expressed in immune tissues under healthy conditions, and their expression was induced by a bacterial challenge, although certain inhibitions were observed after viral and parasitic infections. In the case of the viral challenge, il18 downregulations did not seem to be due to the effect of type I IFNs. CI - Copyright (c) 2021. Published by Elsevier Ltd. FAU - Pereiro, Patricia AU - Pereiro P AD - Instituto de Investigaciones Marinas (IIM), Consejo Superior de Investigaciones Cientificas (CSIC), C/ Eduardo Cabello 6, 36208, Vigo, Spain. FAU - Lama, Raquel AU - Lama R AD - Instituto de Investigaciones Marinas (IIM), Consejo Superior de Investigaciones Cientificas (CSIC), C/ Eduardo Cabello 6, 36208, Vigo, Spain. FAU - Figueras, Antonio AU - Figueras A AD - Instituto de Investigaciones Marinas (IIM), Consejo Superior de Investigaciones Cientificas (CSIC), C/ Eduardo Cabello 6, 36208, Vigo, Spain. FAU - Novoa, Beatriz AU - Novoa B AD - Instituto de Investigaciones Marinas (IIM), Consejo Superior de Investigaciones Cientificas (CSIC), C/ Eduardo Cabello 6, 36208, Vigo, Spain. Electronic address: beatriznovoa@iim.csic.es. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210703 PL - United States TA - Dev Comp Immunol JT - Developmental and comparative immunology JID - 7708205 RN - 0 (Fish Proteins) RN - 0 (Interferon Type I) RN - 0 (Interleukin-18) RN - 0 (Protein Isoforms) SB - IM MH - Aeromonas salmonicida/pathogenicity MH - Alternative Splicing MH - Animals MH - Fish Diseases/immunology/microbiology/parasitology/virology MH - Fish Proteins/genetics/immunology MH - Flatfishes/genetics/*immunology MH - Gene Expression MH - Interferon Type I/immunology MH - Interleukin-18/*genetics/*immunology MH - Novirhabdovirus/pathogenicity MH - Oligohymenophorea/pathogenicity MH - Phylogeny MH - Protein Isoforms MH - Synteny MH - Tissue Distribution OTO - NOTNLM OT - Immune response OT - Interleukin-18 OT - Splicing variants OT - Teleost OT - Turbot EDAT- 2021/07/07 06:00 MHDA- 2022/03/25 06:00 CRDT- 2021/07/06 20:11 PHST- 2021/06/07 00:00 [received] PHST- 2021/07/02 00:00 [revised] PHST- 2021/07/02 00:00 [accepted] PHST- 2021/07/07 06:00 [pubmed] PHST- 2022/03/25 06:00 [medline] PHST- 2021/07/06 20:11 [entrez] AID - S0145-305X(21)00207-X [pii] AID - 10.1016/j.dci.2021.104199 [doi] PST - ppublish SO - Dev Comp Immunol. 2021 Nov;124:104199. doi: 10.1016/j.dci.2021.104199. Epub 2021 Jul 3.