Immunostimulatory DNA
Nucleotide sequences containing CpG-motifs are recognized as immunomodulators in pigs among other species. Phosphodiester oligodeoxynucleotides (ODNs), such as ODN H, have been demonstrated to be potent inducers of interferon-alpha (INF-alpha) in porcine blood mononuclear cells (poPBMC) provided the...
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| Formato: | Otro |
| Lenguaje: | sueco Inglés |
| Publicado: |
2006
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| Acceso en línea: | https://stud.epsilon.slu.se/11068/ |
| _version_ | 1855571802257883136 |
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| author | Elving, Josefine |
| author_browse | Elving, Josefine |
| author_facet | Elving, Josefine |
| author_sort | Elving, Josefine |
| collection | Epsilon Archive for Student Projects |
| description | Nucleotide sequences containing CpG-motifs are recognized as immunomodulators in pigs among other species. Phosphodiester oligodeoxynucleotides (ODNs), such as ODN H, have been demonstrated to be potent inducers of interferon-alpha (INF-alpha) in porcine blood mononuclear cells (poPBMC) provided they are pre-treated with Lipofectin®. In the present study the IFN-alpha inducing activity of ODN H was demonstrated to be altered after addition of poly-G sequences at the 5' and/or 3' end and by increasing the number of nucleotides (nt) in the base-pairing sequence of the ODN. Alterations that facilitated the formation of secondary structures reduced the need for pre-treatment with Lipofectin®. Furthermore, deliberate destruction of secondary structures by heat-treatment of ODN 2216 reduced the IFN-alpha inducing capacity of that ODN. Thus, results suggest that the stimulatory activity of the ODNs is dependent on secondary structure formation. Other ODNs are recognized as potent inhibitors of the INF-alpha production in poPBMC. The ODN PCV2/1 corresponding to a 20 nt long sequence from the genome of PCV2, has been identified as such an inhibitory ODN. Further, it was demonstrated that the inhibitory capacity of ODN PCV2/1 not depend on the presence of a central CpG-motif. Further, results from the in vitro studies show a significant difference between ODN PCV2/1 found in the genome of PCV2 from healthy pigs in Sweden and ODN PCV2/1S1, which predominates in pigs from farms with PMWS in Sweden. However, the biological significance of these findings remain to be elucidated. |
| format | Otro |
| id | RepoSLU11068 |
| institution | Swedish University of Agricultural Sciences |
| language | Swedish Inglés |
| publishDate | 2006 |
| publishDateSort | 2006 |
| record_format | eprints |
| spelling | RepoSLU110682017-10-02T07:27:23Z https://stud.epsilon.slu.se/11068/ Immunostimulatory DNA Elving, Josefine Dept. of Molecular Biosciences Nucleotide sequences containing CpG-motifs are recognized as immunomodulators in pigs among other species. Phosphodiester oligodeoxynucleotides (ODNs), such as ODN H, have been demonstrated to be potent inducers of interferon-alpha (INF-alpha) in porcine blood mononuclear cells (poPBMC) provided they are pre-treated with Lipofectin®. In the present study the IFN-alpha inducing activity of ODN H was demonstrated to be altered after addition of poly-G sequences at the 5' and/or 3' end and by increasing the number of nucleotides (nt) in the base-pairing sequence of the ODN. Alterations that facilitated the formation of secondary structures reduced the need for pre-treatment with Lipofectin®. Furthermore, deliberate destruction of secondary structures by heat-treatment of ODN 2216 reduced the IFN-alpha inducing capacity of that ODN. Thus, results suggest that the stimulatory activity of the ODNs is dependent on secondary structure formation. Other ODNs are recognized as potent inhibitors of the INF-alpha production in poPBMC. The ODN PCV2/1 corresponding to a 20 nt long sequence from the genome of PCV2, has been identified as such an inhibitory ODN. Further, it was demonstrated that the inhibitory capacity of ODN PCV2/1 not depend on the presence of a central CpG-motif. Further, results from the in vitro studies show a significant difference between ODN PCV2/1 found in the genome of PCV2 from healthy pigs in Sweden and ODN PCV2/1S1, which predominates in pigs from farms with PMWS in Sweden. However, the biological significance of these findings remain to be elucidated. Nukleotidsekvenser i mikrobiellt DNA som innehåller CpG-motiv kan fungera som immumodulatorer hos bl.a. gris. För att efterlikna detta in vitro kan man använda sig av oligodeoxynukleotider (ODN). Vissa fosfodiester ODN, såsom ODN H, har visat sig kunna aktivera vita blodkroppar så att de producerar interferon-alfa (IFN-a) förutsatt att oligodeoxynukleotiderna förbehandlats med Lipofektin®. Denna studie visar att den IFN-a inducerande förmågan hos ODN H kan förändras genom tillsats av poly-G sekvenser till 5’ och/eller 3’ änden samt genom en ökning av antalet nukleotider i den basparande sträckan. För att undersöka hur den stimulatoriska aktiviteten påverkas av denaturering utfördes studier på ODN 2216, som har förmågan att baspara med sig själv. Resultaten visade på en minskning av den IFN-a inducerande aktiviteten efter denaturering vilket tyder på att den stimulatoriska aktiviteten hos en ODN är beroende av formation av sekundärstrukturer. Andra ODN har visat sig kunna inhiberar IFN-a produktionen från vita blodkroppar, till dessa hör ODN PCV2/1 som motsvarar en 20 nt lång sekvens som återfinns i genomet hos porcint circovirus typ 2 (PCV2) hos friska grisar i Sverige. In vitro studien visar att det centrala CpG-motivet inte är nödvändigt för den inhiberande förmågan hos ODN PCV2/1. Studien visar dock på en signifikant skillnad mellan den IFN-a inhiberande kapaciten hos ODN PCV2/1 och ODN PCV2/1S1, som dominerar bland grisar från svenska besättningar med PMWS och saknar det centrala CpG-motivet. Det kvarstår dock att klarlägga den bilogiska relevansen av dessa fynd. 2006-07-25 Other NonPeerReviewed application/pdf sv https://stud.epsilon.slu.se/11068/1/elving_j_171002.pdf Elving, Josefine, 2006. Immunostimulatory DNA : studies on the importance of secondary structure formation and CpG-motifs for IFN-alpha induction/inhibition using ODNs related to the genome of porcine circovirus type 2. UNSPECIFIED, Uppsala. Uppsala: (VH) > Dept. of Molecular Biosciences <https://stud.epsilon.slu.se/view/divisions/7040.html> urn:nbn:se:slu:epsilon-s-7320 eng |
| spellingShingle | Dept. of Molecular Biosciences Elving, Josefine Immunostimulatory DNA |
| title | Immunostimulatory DNA |
| title_full | Immunostimulatory DNA |
| title_fullStr | Immunostimulatory DNA |
| title_full_unstemmed | Immunostimulatory DNA |
| title_short | Immunostimulatory DNA |
| title_sort | immunostimulatory dna |
| topic | Dept. of Molecular Biosciences |
| url | https://stud.epsilon.slu.se/11068/ https://stud.epsilon.slu.se/11068/ |