The mtDNA nt7778 G/T polymorphism augments formation of lymphocytic foci but does not aggravate cerulein-induced acute pancreatitis in mice.
A polymorphism in the ATP synthase 8 (ATP8) gene of the murine mitochondrial genome, G-to-T transversion at position 7778, has been suggested to increase susceptibility to multiple autoimmune diseases, including autoimmune pancreatitis (AIP). The polymorphism also induces mitochondrial reactive oxyg...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4092110?pdf=render |
| _version_ | 1818525675868389376 |
|---|---|
| author | Sarah Müller Burkhard Krüger Falko Lange Cristin N Bock Horst Nizze Änne Glass Saleh M Ibrahim Robert Jaster |
| author_facet | Sarah Müller Burkhard Krüger Falko Lange Cristin N Bock Horst Nizze Änne Glass Saleh M Ibrahim Robert Jaster |
| author_sort | Sarah Müller |
| collection | DOAJ |
| description | A polymorphism in the ATP synthase 8 (ATP8) gene of the murine mitochondrial genome, G-to-T transversion at position 7778, has been suggested to increase susceptibility to multiple autoimmune diseases, including autoimmune pancreatitis (AIP). The polymorphism also induces mitochondrial reactive oxygen species generation, secretory dysfunction and β-cell mass adaptation. Here, we have used two conplastic mouse strains, C57BL/6N-mtAKR/J (B6-mtAKR; nt7778 G; control) and C57BL/6N-mtFVB/N (B6-mtFVB; nt7778 T), to address the question if the polymorphism also affects the course of cerulein-induced acute pancreatitis in mice. Therefore, two age groups of mice (3 and 12-month-old, respectively) were subjected to up to 7 injections of the secretagogue cerulein (50 µg/kg body weight) at hourly intervals. Disease severity was assessed at time points from 3 hours to 7 days based on pancreatic histopathology, serum levels of α-amylase and activities of myeloperoxidase (MPO) in lung tissue. A comparison of cerulein-induced pancreatic tissue damage and increases of α-amylase and MPO activities showed no differences between the age-matched groups of both strains. Interestingly, histological evaluation of pancreatic tissue of both untreated and cerulein-treated B6-mtAKR and B6-mtFVB mice also revealed the presence of infiltrates of immune cells surrounding ducts and vessels; a finding that is compatible with an early stage of AIP. After recovery from cerulein-induced pancreatitis (day 7 after the injections), 12-month-old B6-mtFVB mice but not B6-mtAKR mice displayed aggravated lymphocytic lesions. A comparison of 12-month-old mice with other age groups of both strains revealed that lymphocytic foci were largely absent in 3-month-old mice, while 24-month-old mice were more affected. Together, our data suggest that the mtDNA nt7778 G/T polymorphism does not aggravate cerulein-induced acute pancreatitis. Autoimmune-like lesions, however, may progress faster if additional tissue damage occurs. |
| first_indexed | 2024-12-11T06:12:06Z |
| format | Article |
| id | doaj.art-22dfae1a7a804c18a7d859ec3029c2b0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T06:12:06Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-22dfae1a7a804c18a7d859ec3029c2b02022-12-22T01:18:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10226610.1371/journal.pone.0102266The mtDNA nt7778 G/T polymorphism augments formation of lymphocytic foci but does not aggravate cerulein-induced acute pancreatitis in mice.Sarah MüllerBurkhard KrügerFalko LangeCristin N BockHorst NizzeÄnne GlassSaleh M IbrahimRobert JasterA polymorphism in the ATP synthase 8 (ATP8) gene of the murine mitochondrial genome, G-to-T transversion at position 7778, has been suggested to increase susceptibility to multiple autoimmune diseases, including autoimmune pancreatitis (AIP). The polymorphism also induces mitochondrial reactive oxygen species generation, secretory dysfunction and β-cell mass adaptation. Here, we have used two conplastic mouse strains, C57BL/6N-mtAKR/J (B6-mtAKR; nt7778 G; control) and C57BL/6N-mtFVB/N (B6-mtFVB; nt7778 T), to address the question if the polymorphism also affects the course of cerulein-induced acute pancreatitis in mice. Therefore, two age groups of mice (3 and 12-month-old, respectively) were subjected to up to 7 injections of the secretagogue cerulein (50 µg/kg body weight) at hourly intervals. Disease severity was assessed at time points from 3 hours to 7 days based on pancreatic histopathology, serum levels of α-amylase and activities of myeloperoxidase (MPO) in lung tissue. A comparison of cerulein-induced pancreatic tissue damage and increases of α-amylase and MPO activities showed no differences between the age-matched groups of both strains. Interestingly, histological evaluation of pancreatic tissue of both untreated and cerulein-treated B6-mtAKR and B6-mtFVB mice also revealed the presence of infiltrates of immune cells surrounding ducts and vessels; a finding that is compatible with an early stage of AIP. After recovery from cerulein-induced pancreatitis (day 7 after the injections), 12-month-old B6-mtFVB mice but not B6-mtAKR mice displayed aggravated lymphocytic lesions. A comparison of 12-month-old mice with other age groups of both strains revealed that lymphocytic foci were largely absent in 3-month-old mice, while 24-month-old mice were more affected. Together, our data suggest that the mtDNA nt7778 G/T polymorphism does not aggravate cerulein-induced acute pancreatitis. Autoimmune-like lesions, however, may progress faster if additional tissue damage occurs.http://europepmc.org/articles/PMC4092110?pdf=render |
| spellingShingle | Sarah Müller Burkhard Krüger Falko Lange Cristin N Bock Horst Nizze Änne Glass Saleh M Ibrahim Robert Jaster The mtDNA nt7778 G/T polymorphism augments formation of lymphocytic foci but does not aggravate cerulein-induced acute pancreatitis in mice. PLoS ONE |
| title | The mtDNA nt7778 G/T polymorphism augments formation of lymphocytic foci but does not aggravate cerulein-induced acute pancreatitis in mice. |
| title_full | The mtDNA nt7778 G/T polymorphism augments formation of lymphocytic foci but does not aggravate cerulein-induced acute pancreatitis in mice. |
| title_fullStr | The mtDNA nt7778 G/T polymorphism augments formation of lymphocytic foci but does not aggravate cerulein-induced acute pancreatitis in mice. |
| title_full_unstemmed | The mtDNA nt7778 G/T polymorphism augments formation of lymphocytic foci but does not aggravate cerulein-induced acute pancreatitis in mice. |
| title_short | The mtDNA nt7778 G/T polymorphism augments formation of lymphocytic foci but does not aggravate cerulein-induced acute pancreatitis in mice. |
| title_sort | mtdna nt7778 g t polymorphism augments formation of lymphocytic foci but does not aggravate cerulein induced acute pancreatitis in mice |
| url | http://europepmc.org/articles/PMC4092110?pdf=render |
| work_keys_str_mv | AT sarahmuller themtdnant7778gtpolymorphismaugmentsformationoflymphocyticfocibutdoesnotaggravateceruleininducedacutepancreatitisinmice AT burkhardkruger themtdnant7778gtpolymorphismaugmentsformationoflymphocyticfocibutdoesnotaggravateceruleininducedacutepancreatitisinmice AT falkolange themtdnant7778gtpolymorphismaugmentsformationoflymphocyticfocibutdoesnotaggravateceruleininducedacutepancreatitisinmice AT cristinnbock themtdnant7778gtpolymorphismaugmentsformationoflymphocyticfocibutdoesnotaggravateceruleininducedacutepancreatitisinmice AT horstnizze themtdnant7778gtpolymorphismaugmentsformationoflymphocyticfocibutdoesnotaggravateceruleininducedacutepancreatitisinmice AT anneglass themtdnant7778gtpolymorphismaugmentsformationoflymphocyticfocibutdoesnotaggravateceruleininducedacutepancreatitisinmice AT salehmibrahim themtdnant7778gtpolymorphismaugmentsformationoflymphocyticfocibutdoesnotaggravateceruleininducedacutepancreatitisinmice AT robertjaster themtdnant7778gtpolymorphismaugmentsformationoflymphocyticfocibutdoesnotaggravateceruleininducedacutepancreatitisinmice AT sarahmuller mtdnant7778gtpolymorphismaugmentsformationoflymphocyticfocibutdoesnotaggravateceruleininducedacutepancreatitisinmice AT burkhardkruger mtdnant7778gtpolymorphismaugmentsformationoflymphocyticfocibutdoesnotaggravateceruleininducedacutepancreatitisinmice AT falkolange mtdnant7778gtpolymorphismaugmentsformationoflymphocyticfocibutdoesnotaggravateceruleininducedacutepancreatitisinmice AT cristinnbock mtdnant7778gtpolymorphismaugmentsformationoflymphocyticfocibutdoesnotaggravateceruleininducedacutepancreatitisinmice AT horstnizze mtdnant7778gtpolymorphismaugmentsformationoflymphocyticfocibutdoesnotaggravateceruleininducedacutepancreatitisinmice AT anneglass mtdnant7778gtpolymorphismaugmentsformationoflymphocyticfocibutdoesnotaggravateceruleininducedacutepancreatitisinmice AT salehmibrahim mtdnant7778gtpolymorphismaugmentsformationoflymphocyticfocibutdoesnotaggravateceruleininducedacutepancreatitisinmice AT robertjaster mtdnant7778gtpolymorphismaugmentsformationoflymphocyticfocibutdoesnotaggravateceruleininducedacutepancreatitisinmice |