Transforming growth factor-β1b

a second TGF-β1 paralogue in the rainbow trout (Oncorhynchus mykiss) that has a lower constitutive expression but is more responsive to immune stimulation

Tanja Maehr, Maria M Costa, Jose L González Vecino, Simon Wadsworth, Samuel A M Martin, Tiehui Wang, Christopher J Secombes

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The rainbow trout (Oncorhynchus mykiss) TGF-β1 sequence was one of the first fish cytokines described. Studies of its expression suggest it is constitutively expressed but displays refractory inducibility. Here we describe a second TGF-β1 (TGF-β1b) gene that is novel in several respects. TGF-β1b possesses typical TGF-β features, including a CXC motif and an integrin binding site, a tetrabasic cut site and a mature peptide of 112 amino acids (aa) containing nine conserved cysteine residues. The mature peptide is 83% identical to the first TGF-β1 sequence described in rainbow trout, that we designate TGF-β1a, and relative to TGF-β1a shows higher homology to Atlantic salmon TGF-β1b, zebrafish TGF-β1a, and sea bass and seabream TGF-β1. The gene organisation of salmonid TGF-β1b genes, as inferred from Atlantic salmon whole genome shotgun contigs, is a 6 exon/5 intron structure with exons 3 and 4 of salmonid TGF-β1a genes apparently fused together. The two trout TGF-β1 genes have a wide distribution in vivo, with highest expression found in immune tissues for both isoforms indicating that TGF-β1 has a predominant role in immunity of fish. Expression of both genes was also seen during the ontogeny of trout, with TGF-β1a relatively constant in expression level but TGF-β1b increasing over time. Immune responses in head kidney (HK) macrophages induced by pathogen associated molecular patterns (PAMPs), pro-inflammatory cytokines, mitogens and pathway activators highly elevated the expression level of TGF-β1b but not that of TGF-β1a. TGF-β1b expression was also increased by polyinosinic:polycytidylic acid (poly(I:C)) and/or lipopolysaccharide (LPS) stimulation in three different trout cell lines studied. Finally we show that TGF-β1b is potentially involved in defense against infection with viral haemorrhagic septicemia virus (VHSV), which had no effect on TGF-β1a expression. Thus, it is likely the TGF-β1b gene represents a copy which fulfils the major immune orchestrating functions of TGF-β1 as seen in other vertebrates.
Original languageEnglish
Pages (from-to)420-432
Number of pages13
JournalFish & Shellfish Immunology
Volume34
Issue number2
Early online date23 Nov 2012
DOIs
Publication statusPublished - Feb 2013

Fingerprint

transforming growth factors
Transforming Growth Factors
rainbow
Oncorhynchus mykiss
Genes
gene
trout
genes
salmonid
Salmo salar
exons
peptide
cytokines
peptides
Fish
Viral hemorrhagic septicemia virus
polyinosinic-polycytidylic acid
Exons
Sparidae
integrins

Keywords

  • animals
  • base sequence
  • cytokines
  • fish diseases
  • gene components
  • gene expression profiling
  • gene expression regulation, developmental
  • head kidney
  • lipopolysaccharides
  • mitogens
  • molecular sequence data
  • novirhabdovirus
  • Oncorhynchus mykiss
  • poly I-C
  • rhabdoviridae infections
  • sequence analysis, DNA
  • species specificity
  • transforming growth factor beta1
  • rainbow trout
  • TGF-β
  • macrophage
  • LPS
  • VHSV

Cite this

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title = "Transforming growth factor-β1b: a second TGF-β1 paralogue in the rainbow trout (Oncorhynchus mykiss) that has a lower constitutive expression but is more responsive to immune stimulation",
abstract = "The rainbow trout (Oncorhynchus mykiss) TGF-β1 sequence was one of the first fish cytokines described. Studies of its expression suggest it is constitutively expressed but displays refractory inducibility. Here we describe a second TGF-β1 (TGF-β1b) gene that is novel in several respects. TGF-β1b possesses typical TGF-β features, including a CXC motif and an integrin binding site, a tetrabasic cut site and a mature peptide of 112 amino acids (aa) containing nine conserved cysteine residues. The mature peptide is 83{\%} identical to the first TGF-β1 sequence described in rainbow trout, that we designate TGF-β1a, and relative to TGF-β1a shows higher homology to Atlantic salmon TGF-β1b, zebrafish TGF-β1a, and sea bass and seabream TGF-β1. The gene organisation of salmonid TGF-β1b genes, as inferred from Atlantic salmon whole genome shotgun contigs, is a 6 exon/5 intron structure with exons 3 and 4 of salmonid TGF-β1a genes apparently fused together. The two trout TGF-β1 genes have a wide distribution in vivo, with highest expression found in immune tissues for both isoforms indicating that TGF-β1 has a predominant role in immunity of fish. Expression of both genes was also seen during the ontogeny of trout, with TGF-β1a relatively constant in expression level but TGF-β1b increasing over time. Immune responses in head kidney (HK) macrophages induced by pathogen associated molecular patterns (PAMPs), pro-inflammatory cytokines, mitogens and pathway activators highly elevated the expression level of TGF-β1b but not that of TGF-β1a. TGF-β1b expression was also increased by polyinosinic:polycytidylic acid (poly(I:C)) and/or lipopolysaccharide (LPS) stimulation in three different trout cell lines studied. Finally we show that TGF-β1b is potentially involved in defense against infection with viral haemorrhagic septicemia virus (VHSV), which had no effect on TGF-β1a expression. Thus, it is likely the TGF-β1b gene represents a copy which fulfils the major immune orchestrating functions of TGF-β1 as seen in other vertebrates.",
keywords = "animals, base sequence, cytokines, fish diseases, gene components, gene expression profiling, gene expression regulation, developmental, head kidney, lipopolysaccharides, mitogens, molecular sequence data, novirhabdovirus, Oncorhynchus mykiss, poly I-C, rhabdoviridae infections, sequence analysis, DNA, species specificity, transforming growth factor beta1, rainbow trout, TGF-β, macrophage, LPS, VHSV",
author = "Tanja Maehr and Costa, {Maria M} and Vecino, {Jose L Gonz{\'a}lez} and Simon Wadsworth and Martin, {Samuel A M} and Tiehui Wang and Secombes, {Christopher J}",
note = "Copyright {\circledC} 2012 Elsevier Ltd. All rights reserved.",
year = "2013",
month = "2",
doi = "10.1016/j.fsi.2012.11.011",
language = "English",
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pages = "420--432",
journal = "Fish & Shellfish Immunology",
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TY - JOUR

T1 - Transforming growth factor-β1b

T2 - a second TGF-β1 paralogue in the rainbow trout (Oncorhynchus mykiss) that has a lower constitutive expression but is more responsive to immune stimulation

AU - Maehr, Tanja

AU - Costa, Maria M

AU - Vecino, Jose L González

AU - Wadsworth, Simon

AU - Martin, Samuel A M

AU - Wang, Tiehui

AU - Secombes, Christopher J

N1 - Copyright © 2012 Elsevier Ltd. All rights reserved.

PY - 2013/2

Y1 - 2013/2

N2 - The rainbow trout (Oncorhynchus mykiss) TGF-β1 sequence was one of the first fish cytokines described. Studies of its expression suggest it is constitutively expressed but displays refractory inducibility. Here we describe a second TGF-β1 (TGF-β1b) gene that is novel in several respects. TGF-β1b possesses typical TGF-β features, including a CXC motif and an integrin binding site, a tetrabasic cut site and a mature peptide of 112 amino acids (aa) containing nine conserved cysteine residues. The mature peptide is 83% identical to the first TGF-β1 sequence described in rainbow trout, that we designate TGF-β1a, and relative to TGF-β1a shows higher homology to Atlantic salmon TGF-β1b, zebrafish TGF-β1a, and sea bass and seabream TGF-β1. The gene organisation of salmonid TGF-β1b genes, as inferred from Atlantic salmon whole genome shotgun contigs, is a 6 exon/5 intron structure with exons 3 and 4 of salmonid TGF-β1a genes apparently fused together. The two trout TGF-β1 genes have a wide distribution in vivo, with highest expression found in immune tissues for both isoforms indicating that TGF-β1 has a predominant role in immunity of fish. Expression of both genes was also seen during the ontogeny of trout, with TGF-β1a relatively constant in expression level but TGF-β1b increasing over time. Immune responses in head kidney (HK) macrophages induced by pathogen associated molecular patterns (PAMPs), pro-inflammatory cytokines, mitogens and pathway activators highly elevated the expression level of TGF-β1b but not that of TGF-β1a. TGF-β1b expression was also increased by polyinosinic:polycytidylic acid (poly(I:C)) and/or lipopolysaccharide (LPS) stimulation in three different trout cell lines studied. Finally we show that TGF-β1b is potentially involved in defense against infection with viral haemorrhagic septicemia virus (VHSV), which had no effect on TGF-β1a expression. Thus, it is likely the TGF-β1b gene represents a copy which fulfils the major immune orchestrating functions of TGF-β1 as seen in other vertebrates.

AB - The rainbow trout (Oncorhynchus mykiss) TGF-β1 sequence was one of the first fish cytokines described. Studies of its expression suggest it is constitutively expressed but displays refractory inducibility. Here we describe a second TGF-β1 (TGF-β1b) gene that is novel in several respects. TGF-β1b possesses typical TGF-β features, including a CXC motif and an integrin binding site, a tetrabasic cut site and a mature peptide of 112 amino acids (aa) containing nine conserved cysteine residues. The mature peptide is 83% identical to the first TGF-β1 sequence described in rainbow trout, that we designate TGF-β1a, and relative to TGF-β1a shows higher homology to Atlantic salmon TGF-β1b, zebrafish TGF-β1a, and sea bass and seabream TGF-β1. The gene organisation of salmonid TGF-β1b genes, as inferred from Atlantic salmon whole genome shotgun contigs, is a 6 exon/5 intron structure with exons 3 and 4 of salmonid TGF-β1a genes apparently fused together. The two trout TGF-β1 genes have a wide distribution in vivo, with highest expression found in immune tissues for both isoforms indicating that TGF-β1 has a predominant role in immunity of fish. Expression of both genes was also seen during the ontogeny of trout, with TGF-β1a relatively constant in expression level but TGF-β1b increasing over time. Immune responses in head kidney (HK) macrophages induced by pathogen associated molecular patterns (PAMPs), pro-inflammatory cytokines, mitogens and pathway activators highly elevated the expression level of TGF-β1b but not that of TGF-β1a. TGF-β1b expression was also increased by polyinosinic:polycytidylic acid (poly(I:C)) and/or lipopolysaccharide (LPS) stimulation in three different trout cell lines studied. Finally we show that TGF-β1b is potentially involved in defense against infection with viral haemorrhagic septicemia virus (VHSV), which had no effect on TGF-β1a expression. Thus, it is likely the TGF-β1b gene represents a copy which fulfils the major immune orchestrating functions of TGF-β1 as seen in other vertebrates.

KW - animals

KW - base sequence

KW - cytokines

KW - fish diseases

KW - gene components

KW - gene expression profiling

KW - gene expression regulation, developmental

KW - head kidney

KW - lipopolysaccharides

KW - mitogens

KW - molecular sequence data

KW - novirhabdovirus

KW - Oncorhynchus mykiss

KW - poly I-C

KW - rhabdoviridae infections

KW - sequence analysis, DNA

KW - species specificity

KW - transforming growth factor beta1

KW - rainbow trout

KW - TGF-β

KW - macrophage

KW - LPS

KW - VHSV

U2 - 10.1016/j.fsi.2012.11.011

DO - 10.1016/j.fsi.2012.11.011

M3 - Article

VL - 34

SP - 420

EP - 432

JO - Fish & Shellfish Immunology

JF - Fish & Shellfish Immunology

SN - 1050-4648

IS - 2

ER -