Vitamin D Regulates the Expression of Glucocorticoid Receptors in Blood of Severe Asthmatic Patients
Purpose. Vitamin D (VitD) deficiency is a significant public health concern in many areas around the globe and has been associated with many immune-mediated diseases, including asthma. Severe asthma has been linked to a decreased glucocorticoid receptor (GR) ratio (GR-α/GR-β ratio), indicating stero...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2021/9947370 |
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| author | Bassam Mahboub Saba Al Heialy Mahmood Yaseen Hachim Rakhee K. Ramakrishnan Ashraf Alzaabi Rania Medhat Seliem Laila Ibraheem Salameh Sameen Masooma Toor Fathelrahman Salem Shendi Ola Mohamed Al Ali Basil Khalid Safarini Wafa Taleb Erabia Rabih Halwani Qutayba Hamid |
| author_facet | Bassam Mahboub Saba Al Heialy Mahmood Yaseen Hachim Rakhee K. Ramakrishnan Ashraf Alzaabi Rania Medhat Seliem Laila Ibraheem Salameh Sameen Masooma Toor Fathelrahman Salem Shendi Ola Mohamed Al Ali Basil Khalid Safarini Wafa Taleb Erabia Rabih Halwani Qutayba Hamid |
| author_sort | Bassam Mahboub |
| collection | DOAJ |
| description | Purpose. Vitamin D (VitD) deficiency is a significant public health concern in many areas around the globe and has been associated with many immune-mediated diseases, including asthma. Severe asthma has been linked to a decreased glucocorticoid receptor (GR) ratio (GR-α/GR-β ratio), indicating steroid hyporesponsiveness. Using a combination of in silico and in vivo approaches, we aimed to explore the immunomodulatory effect of VitD on asthmatic patients diagnosed with hypovitaminosis D. Methods. In silico tools were used to identify the regulatory effect of VitD supplementation on GR genes. We measured the expression levels of GR-α and the inactive isoform, GR-β, in the blood of adult asthmatics diagnosed with hypovitaminosis D before and after VitD supplementation. Moreover, the blood levels of inflammatory cytokines associated with asthma severity were determined. Results. Using an in silico approach, we identified specific genes commonly targeted by VitD as well as corticosteroids, the mainstay of asthma therapy. NR3C1 gene encoding GR was found to be significantly upregulated on Th2 CD4 cells and NK cells. Interestingly, blood expression level of NR3C1 was lower in severe asthmatics compared to nonsevere asthmatics and healthy controls, while the blood level of VitD receptor (VDR) was higher. Upon VitD supplementation of severe asthmatic patients, there was a significant increase in the blood levels of GR-α with no change in GR-β mRNA expression. VitD supplementation also suppressed the blood levels of IL-17F and IL-4. Conclusion. VitD may enhance steroid responsiveness by upregulating the expression of steroid receptor GR-α. |
| format | Article |
| id | doaj-art-19ccec72981d49c3996b4c61f1e5c7d9 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-19ccec72981d49c3996b4c61f1e5c7d92025-02-03T01:24:47ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/99473709947370Vitamin D Regulates the Expression of Glucocorticoid Receptors in Blood of Severe Asthmatic PatientsBassam Mahboub0Saba Al Heialy1Mahmood Yaseen Hachim2Rakhee K. Ramakrishnan3Ashraf Alzaabi4Rania Medhat Seliem5Laila Ibraheem Salameh6Sameen Masooma Toor7Fathelrahman Salem Shendi8Ola Mohamed Al Ali9Basil Khalid Safarini10Wafa Taleb Erabia11Rabih Halwani12Qutayba Hamid13Sharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah, UAEDepartment of Basic Medical Sciences, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAEDepartment of Basic Medical Sciences, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAESharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah, UAEZayed Military Hospital, Abu Dhabi, UAERashid Hospital, Dubai Health Authority, Dubai, UAESharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah, UAEZayed Military Hospital, Abu Dhabi, UAERashid Hospital, Dubai Health Authority, Dubai, UAERashid Hospital, Dubai Health Authority, Dubai, UAERashid Hospital, Dubai Health Authority, Dubai, UAERashid Hospital, Dubai Health Authority, Dubai, UAESharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah, UAESharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah, UAEPurpose. Vitamin D (VitD) deficiency is a significant public health concern in many areas around the globe and has been associated with many immune-mediated diseases, including asthma. Severe asthma has been linked to a decreased glucocorticoid receptor (GR) ratio (GR-α/GR-β ratio), indicating steroid hyporesponsiveness. Using a combination of in silico and in vivo approaches, we aimed to explore the immunomodulatory effect of VitD on asthmatic patients diagnosed with hypovitaminosis D. Methods. In silico tools were used to identify the regulatory effect of VitD supplementation on GR genes. We measured the expression levels of GR-α and the inactive isoform, GR-β, in the blood of adult asthmatics diagnosed with hypovitaminosis D before and after VitD supplementation. Moreover, the blood levels of inflammatory cytokines associated with asthma severity were determined. Results. Using an in silico approach, we identified specific genes commonly targeted by VitD as well as corticosteroids, the mainstay of asthma therapy. NR3C1 gene encoding GR was found to be significantly upregulated on Th2 CD4 cells and NK cells. Interestingly, blood expression level of NR3C1 was lower in severe asthmatics compared to nonsevere asthmatics and healthy controls, while the blood level of VitD receptor (VDR) was higher. Upon VitD supplementation of severe asthmatic patients, there was a significant increase in the blood levels of GR-α with no change in GR-β mRNA expression. VitD supplementation also suppressed the blood levels of IL-17F and IL-4. Conclusion. VitD may enhance steroid responsiveness by upregulating the expression of steroid receptor GR-α.http://dx.doi.org/10.1155/2021/9947370 |
| spellingShingle | Bassam Mahboub Saba Al Heialy Mahmood Yaseen Hachim Rakhee K. Ramakrishnan Ashraf Alzaabi Rania Medhat Seliem Laila Ibraheem Salameh Sameen Masooma Toor Fathelrahman Salem Shendi Ola Mohamed Al Ali Basil Khalid Safarini Wafa Taleb Erabia Rabih Halwani Qutayba Hamid Vitamin D Regulates the Expression of Glucocorticoid Receptors in Blood of Severe Asthmatic Patients Journal of Immunology Research |
| title | Vitamin D Regulates the Expression of Glucocorticoid Receptors in Blood of Severe Asthmatic Patients |
| title_full | Vitamin D Regulates the Expression of Glucocorticoid Receptors in Blood of Severe Asthmatic Patients |
| title_fullStr | Vitamin D Regulates the Expression of Glucocorticoid Receptors in Blood of Severe Asthmatic Patients |
| title_full_unstemmed | Vitamin D Regulates the Expression of Glucocorticoid Receptors in Blood of Severe Asthmatic Patients |
| title_short | Vitamin D Regulates the Expression of Glucocorticoid Receptors in Blood of Severe Asthmatic Patients |
| title_sort | vitamin d regulates the expression of glucocorticoid receptors in blood of severe asthmatic patients |
| url | http://dx.doi.org/10.1155/2021/9947370 |
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