Lost and Found: The Family of NF-κB Inhibitors Is Larger than Assumed in Salmonid Fish
NF-κB signalling is largely controlled by the family of ‘inhibitors of NF-κB’ (IκB). The relevant databases indicate that the genome of rainbow trout contains multiple gene copies coding for iκbα (<i>nfkbia</i>), iκbε (<i>nfkbie</i>), iκbδ (<i>nkfbid</i>), iκbζ (&...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-06-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/12/10229 |
| _version_ | 1797594256254173184 |
|---|---|
| author | Doret R. van Muilekom Bertrand Collet Henrike Rebl Kristina Zlatina Fabio Sarais Tom Goldammer Alexander Rebl |
| author_facet | Doret R. van Muilekom Bertrand Collet Henrike Rebl Kristina Zlatina Fabio Sarais Tom Goldammer Alexander Rebl |
| author_sort | Doret R. van Muilekom |
| collection | DOAJ |
| description | NF-κB signalling is largely controlled by the family of ‘inhibitors of NF-κB’ (IκB). The relevant databases indicate that the genome of rainbow trout contains multiple gene copies coding for iκbα (<i>nfkbia</i>), iκbε (<i>nfkbie</i>), iκbδ (<i>nkfbid</i>), iκbζ (<i>nfkbiz</i>), and <i>bcl3</i>, but it lacks iκbβ (<i>nfkbib</i>) and iκbη (<i>ankrd42</i>). Strikingly, three <i>nfkbia</i> paralogs are apparently present in salmonid fish, two of which share a high sequence identity, while the third putative <i>nfkbia</i> gene is significantly less like its two paralogs. This particular <i>nfkbia</i> gene product, iκbα, clusters with the human IκBβ in a phylogenetic analysis, while the other two iκbα proteins from trout associate with their human IκBα counterpart. The transcript concentrations were significantly higher for the structurally more closely related <i>nfkbia</i> paralogs than for the structurally less similar paralog, suggesting that iκbβ probably has not been lost from the salmonid genomes but has been incorrectly designated as iκbα. In the present study, two gene variants coding for iκbα (<i>nfkbia</i>) and iκbε (<i>nfkbie</i>) were prominently expressed in the immune tissues and, particularly, in a cell fraction enriched with granulocytes, monocytes/macrophages, and dendritic cells from the head kidney of rainbow trout. Stimulation of salmonid CHSE-214 cells with zymosan significantly upregulated the iκbα-encoding gene while elevating the copy numbers of the inflammatory markers interleukin-1-beta and interleukin-8. Overexpression of iκbα and iκbε in CHSE-214 cells dose-dependently quenched both the basal and stimulated activity of an NF-κB promoter suggesting their involvement in immune-regulatory processes. This study provides the first functional data on iκbε—versus the well-researched iκbα factor—in a non-mammalian model species. |
| first_indexed | 2024-03-11T02:21:01Z |
| format | Article |
| id | doaj.art-1367fec24cd44661a4738201714c4600 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T02:21:01Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1367fec24cd44661a4738201714c46002023-11-18T10:50:34ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124121022910.3390/ijms241210229Lost and Found: The Family of NF-κB Inhibitors Is Larger than Assumed in Salmonid FishDoret R. van Muilekom0Bertrand Collet1Henrike Rebl2Kristina Zlatina3Fabio Sarais4Tom Goldammer5Alexander Rebl6Institute of Genome Biology, Research Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, GermanyVIM, UVSQ, INRAE, Université Paris-Saclay, 78350 Jouy-en-Josas, FranceDepartment of Cell Biology, Rostock University Medical Center, 18057 Rostock, GermanyInstitute of Reproductive Biology, Research Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, GermanyInstitute of Genome Biology, Research Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, GermanyInstitute of Genome Biology, Research Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, GermanyInstitute of Genome Biology, Research Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, GermanyNF-κB signalling is largely controlled by the family of ‘inhibitors of NF-κB’ (IκB). The relevant databases indicate that the genome of rainbow trout contains multiple gene copies coding for iκbα (<i>nfkbia</i>), iκbε (<i>nfkbie</i>), iκbδ (<i>nkfbid</i>), iκbζ (<i>nfkbiz</i>), and <i>bcl3</i>, but it lacks iκbβ (<i>nfkbib</i>) and iκbη (<i>ankrd42</i>). Strikingly, three <i>nfkbia</i> paralogs are apparently present in salmonid fish, two of which share a high sequence identity, while the third putative <i>nfkbia</i> gene is significantly less like its two paralogs. This particular <i>nfkbia</i> gene product, iκbα, clusters with the human IκBβ in a phylogenetic analysis, while the other two iκbα proteins from trout associate with their human IκBα counterpart. The transcript concentrations were significantly higher for the structurally more closely related <i>nfkbia</i> paralogs than for the structurally less similar paralog, suggesting that iκbβ probably has not been lost from the salmonid genomes but has been incorrectly designated as iκbα. In the present study, two gene variants coding for iκbα (<i>nfkbia</i>) and iκbε (<i>nfkbie</i>) were prominently expressed in the immune tissues and, particularly, in a cell fraction enriched with granulocytes, monocytes/macrophages, and dendritic cells from the head kidney of rainbow trout. Stimulation of salmonid CHSE-214 cells with zymosan significantly upregulated the iκbα-encoding gene while elevating the copy numbers of the inflammatory markers interleukin-1-beta and interleukin-8. Overexpression of iκbα and iκbε in CHSE-214 cells dose-dependently quenched both the basal and stimulated activity of an NF-κB promoter suggesting their involvement in immune-regulatory processes. This study provides the first functional data on iκbε—versus the well-researched iκbα factor—in a non-mammalian model species.https://www.mdpi.com/1422-0067/24/12/10229IκBinnate immunityimmune regulationNF-κBnfkbianfkbie |
| spellingShingle | Doret R. van Muilekom Bertrand Collet Henrike Rebl Kristina Zlatina Fabio Sarais Tom Goldammer Alexander Rebl Lost and Found: The Family of NF-κB Inhibitors Is Larger than Assumed in Salmonid Fish International Journal of Molecular Sciences IκB innate immunity immune regulation NF-κB nfkbia nfkbie |
| title | Lost and Found: The Family of NF-κB Inhibitors Is Larger than Assumed in Salmonid Fish |
| title_full | Lost and Found: The Family of NF-κB Inhibitors Is Larger than Assumed in Salmonid Fish |
| title_fullStr | Lost and Found: The Family of NF-κB Inhibitors Is Larger than Assumed in Salmonid Fish |
| title_full_unstemmed | Lost and Found: The Family of NF-κB Inhibitors Is Larger than Assumed in Salmonid Fish |
| title_short | Lost and Found: The Family of NF-κB Inhibitors Is Larger than Assumed in Salmonid Fish |
| title_sort | lost and found the family of nf κb inhibitors is larger than assumed in salmonid fish |
| topic | IκB innate immunity immune regulation NF-κB nfkbia nfkbie |
| url | https://www.mdpi.com/1422-0067/24/12/10229 |
| work_keys_str_mv | AT doretrvanmuilekom lostandfoundthefamilyofnfkbinhibitorsislargerthanassumedinsalmonidfish AT bertrandcollet lostandfoundthefamilyofnfkbinhibitorsislargerthanassumedinsalmonidfish AT henrikerebl lostandfoundthefamilyofnfkbinhibitorsislargerthanassumedinsalmonidfish AT kristinazlatina lostandfoundthefamilyofnfkbinhibitorsislargerthanassumedinsalmonidfish AT fabiosarais lostandfoundthefamilyofnfkbinhibitorsislargerthanassumedinsalmonidfish AT tomgoldammer lostandfoundthefamilyofnfkbinhibitorsislargerthanassumedinsalmonidfish AT alexanderrebl lostandfoundthefamilyofnfkbinhibitorsislargerthanassumedinsalmonidfish |