Decrease in alpha-1 antiproteinase antitrypsin is observed in primary Sjogren’s syndrome condition
Primary Sjogren’s syndrome (pSS) is a systemic autoimmune disease that is characterized by the infiltration of immune cells. Although the loss of salivary gland function is a major manifestation observed in pSS, the factors that could promote these changes in salivary gland tissue in pSS is not yet...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-07-01
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| Series: | Autoimmunity |
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| Online Access: | http://dx.doi.org/10.1080/08916934.2020.1768376 |
| _version_ | 1797684743297302528 |
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| author | Brij B. Singh Joyce Ohm Fredice O. Quenum Zanbede Pooja Chauhan Frans G. M. Kroese Arjan Vissink Julian L. Ambrus Bibhuti B. Mishra |
| author_facet | Brij B. Singh Joyce Ohm Fredice O. Quenum Zanbede Pooja Chauhan Frans G. M. Kroese Arjan Vissink Julian L. Ambrus Bibhuti B. Mishra |
| author_sort | Brij B. Singh |
| collection | DOAJ |
| description | Primary Sjogren’s syndrome (pSS) is a systemic autoimmune disease that is characterized by the infiltration of immune cells. Although the loss of salivary gland function is a major manifestation observed in pSS, the factors that could promote these changes in salivary gland tissue in pSS is not yet determined. Herein, we provide evidence that loss of alpha-1 antiproteinase antitrypsin could contribute to the induction of pSS. Alpha-1 antiproteinase antitrypsin belongs to the family of serpin proteins that function as protease inhibitors and protect secretory cells against proteases, especially to elastases that is secreted from lymphocytes. Importantly, expression of alpha-1 antiproteinase antitrypsin was decreased (more than 3-fold), along with an increase in elastase expression, in pSS samples when compared with age-matched non-SS-SICCA patients. Consistent with the human data, loss of alpha-1 antiproteinase antitrypsin, as well as an increase in immune infiltration, was observed in IL14α transgenic mice that exhibit SS like symptoms. Moreover, an age-dependent increase in elastase expression was observed in IL14α transgenic mice along with a decrease in total saliva secretion. Importantly, a 4-fold increase in microRNA132 expression, but not in other microRNAs, and increased DNA methylation in the promoter/noncoding region of serpina gene was observed in pSS, which could be responsible for the inhibition of alpha-1 antiproteinase antitrypsin expression in salivary gland cells of pSS patients. Together, these findings demonstrate that epigenetic regulations that include DNA methylation and microRNAs that could modulate the expression of alpha-1 antiproteinase antitrypsin in salivary glands and could be involved in the onset of pSS. |
| first_indexed | 2024-03-12T00:34:13Z |
| format | Article |
| id | doaj.art-8452d96d30cf40e4bda70a65f74c559f |
| institution | Directory Open Access Journal |
| issn | 0891-6934 1607-842X |
| language | English |
| last_indexed | 2024-03-12T00:34:13Z |
| publishDate | 2020-07-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autoimmunity |
| spelling | doaj.art-8452d96d30cf40e4bda70a65f74c559f2023-09-15T10:01:09ZengTaylor & Francis GroupAutoimmunity0891-69341607-842X2020-07-0153527028210.1080/08916934.2020.17683761768376Decrease in alpha-1 antiproteinase antitrypsin is observed in primary Sjogren’s syndrome conditionBrij B. Singh0Joyce Ohm1Fredice O. Quenum Zanbede2Pooja Chauhan3Frans G. M. Kroese4Arjan Vissink5Julian L. Ambrus6Bibhuti B. Mishra7School of Dentistry University of Texas Health Science CenterUniversity of North DakotaUniversity of North DakotaUniversity of North DakotaUniversity of Groningen and University Medical Center GroningenUniversity of Groningen and University Medical Center GroningenState University of New YorkSchool of Dentistry University of Texas Health Science CenterPrimary Sjogren’s syndrome (pSS) is a systemic autoimmune disease that is characterized by the infiltration of immune cells. Although the loss of salivary gland function is a major manifestation observed in pSS, the factors that could promote these changes in salivary gland tissue in pSS is not yet determined. Herein, we provide evidence that loss of alpha-1 antiproteinase antitrypsin could contribute to the induction of pSS. Alpha-1 antiproteinase antitrypsin belongs to the family of serpin proteins that function as protease inhibitors and protect secretory cells against proteases, especially to elastases that is secreted from lymphocytes. Importantly, expression of alpha-1 antiproteinase antitrypsin was decreased (more than 3-fold), along with an increase in elastase expression, in pSS samples when compared with age-matched non-SS-SICCA patients. Consistent with the human data, loss of alpha-1 antiproteinase antitrypsin, as well as an increase in immune infiltration, was observed in IL14α transgenic mice that exhibit SS like symptoms. Moreover, an age-dependent increase in elastase expression was observed in IL14α transgenic mice along with a decrease in total saliva secretion. Importantly, a 4-fold increase in microRNA132 expression, but not in other microRNAs, and increased DNA methylation in the promoter/noncoding region of serpina gene was observed in pSS, which could be responsible for the inhibition of alpha-1 antiproteinase antitrypsin expression in salivary gland cells of pSS patients. Together, these findings demonstrate that epigenetic regulations that include DNA methylation and microRNAs that could modulate the expression of alpha-1 antiproteinase antitrypsin in salivary glands and could be involved in the onset of pSS.http://dx.doi.org/10.1080/08916934.2020.1768376dna methylationmicrornasalpha-1 antiproteinase antitrypsinsalivary glandssjogren’s syndrome |
| spellingShingle | Brij B. Singh Joyce Ohm Fredice O. Quenum Zanbede Pooja Chauhan Frans G. M. Kroese Arjan Vissink Julian L. Ambrus Bibhuti B. Mishra Decrease in alpha-1 antiproteinase antitrypsin is observed in primary Sjogren’s syndrome condition Autoimmunity dna methylation micrornas alpha-1 antiproteinase antitrypsin salivary glands sjogren’s syndrome |
| title | Decrease in alpha-1 antiproteinase antitrypsin is observed in primary Sjogren’s syndrome condition |
| title_full | Decrease in alpha-1 antiproteinase antitrypsin is observed in primary Sjogren’s syndrome condition |
| title_fullStr | Decrease in alpha-1 antiproteinase antitrypsin is observed in primary Sjogren’s syndrome condition |
| title_full_unstemmed | Decrease in alpha-1 antiproteinase antitrypsin is observed in primary Sjogren’s syndrome condition |
| title_short | Decrease in alpha-1 antiproteinase antitrypsin is observed in primary Sjogren’s syndrome condition |
| title_sort | decrease in alpha 1 antiproteinase antitrypsin is observed in primary sjogren s syndrome condition |
| topic | dna methylation micrornas alpha-1 antiproteinase antitrypsin salivary glands sjogren’s syndrome |
| url | http://dx.doi.org/10.1080/08916934.2020.1768376 |
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