PARP-1 Is Critical for Recruitment of Dendritic Cells to the Lung in a Mouse Model of Asthma but Dispensable for Their Differentiation and Function
Dendritic cells (DCs) are critical in asthma and many other immune diseases. We previously demonstrated a role for PARP-1 in asthma. Evidence on PARP-1 playing a role in Th2-associated DC function is not clear. In this study, we examined whether PARP-1 is critical for DC differentiation and function...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2019/1656484 |
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| author | Laura C. Echeverri Tirado Mohamed A. Ghonim Jeffrey Wang Amir A. Al-Khami Dorota Wyczechowska Hanh H. Luu Hogyoung Kim Maria Dulfary Sanchez-Pino José Yélamos Lina M. Yassin A. Hamid Boulares |
| author_facet | Laura C. Echeverri Tirado Mohamed A. Ghonim Jeffrey Wang Amir A. Al-Khami Dorota Wyczechowska Hanh H. Luu Hogyoung Kim Maria Dulfary Sanchez-Pino José Yélamos Lina M. Yassin A. Hamid Boulares |
| author_sort | Laura C. Echeverri Tirado |
| collection | DOAJ |
| description | Dendritic cells (DCs) are critical in asthma and many other immune diseases. We previously demonstrated a role for PARP-1 in asthma. Evidence on PARP-1 playing a role in Th2-associated DC function is not clear. In this study, we examined whether PARP-1 is critical for DC differentiation and function using bone marrow progenitors and their migration to the lung in an ovalbumin-based mouse model of asthma. Results show that changes in PARP-1 levels during GM-CSF-induced DC differentiation from bone marrow progenitors were cyclic and appear to be part of an array of changes that included STAT3/STAT5/STAT6/GRAIL/RAD51. Interestingly, PARP-1 gene deletion affected primarily STAT6 and γH2AX. PARP-1 inhibition significantly reduced the migration of DCs to the lungs of ovalbumin-challenged mice, which was associated with a concomitant reduction in lung levels of the adhesion molecule VCAM-1. The requirement of PARP-1 for VCAM-1 expression was confirmed using endothelial and lung smooth muscle cells. PARP-1 expression and activity were also required for VCAM-1 in differentiated DCs. An assessment of CD11b+/CD11c+/MHCIIhigh DCs in spleens and lymph nodes of OVA-sensitized mice revealed that PARP-1 inhibition genetically or by olaparib exerted little to no effect on DC differentiation, percentage of CD80+/CD86+/CD40+-expressing cells, or their capacity to promote proliferation of ovalbumin-primed (OTII) CD4+ T cells. These findings were corroborated using GM-CSF-induced differentiation of DCs from the bone marrow. Surprisingly, the PARP-1−/− DCs exhibited a higher intrinsic capacity to induce OTII CD4+ T cell proliferation in the absence of ovalbumin. Overall, our results show that PARP-1 plays little to no role in DC differentiation and function and that the protective effect of PARP-1 inhibition against asthma is associated with a prevention of DC migration to the lung through a reduction in VCAM-1 expression. Given the current use of PARP inhibitors (e.g., olaparib) in the clinic, the present results may be of interest for the relevant therapies. |
| format | Article |
| id | doaj-art-faee433ef7fe4350833c83181cd266f8 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-faee433ef7fe4350833c83181cd266f82025-02-03T06:00:54ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/16564841656484PARP-1 Is Critical for Recruitment of Dendritic Cells to the Lung in a Mouse Model of Asthma but Dispensable for Their Differentiation and FunctionLaura C. Echeverri Tirado0Mohamed A. Ghonim1Jeffrey Wang2Amir A. Al-Khami3Dorota Wyczechowska4Hanh H. Luu5Hogyoung Kim6Maria Dulfary Sanchez-Pino7José Yélamos8Lina M. Yassin9A. Hamid Boulares10The Stanley Scott Cancer Center/Louisiana Cancer Research Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USAThe Stanley Scott Cancer Center/Louisiana Cancer Research Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USAThe Stanley Scott Cancer Center/Louisiana Cancer Research Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USAThe Stanley Scott Cancer Center/Louisiana Cancer Research Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USAThe Stanley Scott Cancer Center/Louisiana Cancer Research Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USAThe Stanley Scott Cancer Center/Louisiana Cancer Research Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USAThe Stanley Scott Cancer Center/Louisiana Cancer Research Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USAThe Stanley Scott Cancer Center/Louisiana Cancer Research Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USACancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, SpainGrupo de Ciencias Básicas, Escuela de Graduados, Universidad CES, Medellín, ColombiaThe Stanley Scott Cancer Center/Louisiana Cancer Research Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USADendritic cells (DCs) are critical in asthma and many other immune diseases. We previously demonstrated a role for PARP-1 in asthma. Evidence on PARP-1 playing a role in Th2-associated DC function is not clear. In this study, we examined whether PARP-1 is critical for DC differentiation and function using bone marrow progenitors and their migration to the lung in an ovalbumin-based mouse model of asthma. Results show that changes in PARP-1 levels during GM-CSF-induced DC differentiation from bone marrow progenitors were cyclic and appear to be part of an array of changes that included STAT3/STAT5/STAT6/GRAIL/RAD51. Interestingly, PARP-1 gene deletion affected primarily STAT6 and γH2AX. PARP-1 inhibition significantly reduced the migration of DCs to the lungs of ovalbumin-challenged mice, which was associated with a concomitant reduction in lung levels of the adhesion molecule VCAM-1. The requirement of PARP-1 for VCAM-1 expression was confirmed using endothelial and lung smooth muscle cells. PARP-1 expression and activity were also required for VCAM-1 in differentiated DCs. An assessment of CD11b+/CD11c+/MHCIIhigh DCs in spleens and lymph nodes of OVA-sensitized mice revealed that PARP-1 inhibition genetically or by olaparib exerted little to no effect on DC differentiation, percentage of CD80+/CD86+/CD40+-expressing cells, or their capacity to promote proliferation of ovalbumin-primed (OTII) CD4+ T cells. These findings were corroborated using GM-CSF-induced differentiation of DCs from the bone marrow. Surprisingly, the PARP-1−/− DCs exhibited a higher intrinsic capacity to induce OTII CD4+ T cell proliferation in the absence of ovalbumin. Overall, our results show that PARP-1 plays little to no role in DC differentiation and function and that the protective effect of PARP-1 inhibition against asthma is associated with a prevention of DC migration to the lung through a reduction in VCAM-1 expression. Given the current use of PARP inhibitors (e.g., olaparib) in the clinic, the present results may be of interest for the relevant therapies.http://dx.doi.org/10.1155/2019/1656484 |
| spellingShingle | Laura C. Echeverri Tirado Mohamed A. Ghonim Jeffrey Wang Amir A. Al-Khami Dorota Wyczechowska Hanh H. Luu Hogyoung Kim Maria Dulfary Sanchez-Pino José Yélamos Lina M. Yassin A. Hamid Boulares PARP-1 Is Critical for Recruitment of Dendritic Cells to the Lung in a Mouse Model of Asthma but Dispensable for Their Differentiation and Function Mediators of Inflammation |
| title | PARP-1 Is Critical for Recruitment of Dendritic Cells to the Lung in a Mouse Model of Asthma but Dispensable for Their Differentiation and Function |
| title_full | PARP-1 Is Critical for Recruitment of Dendritic Cells to the Lung in a Mouse Model of Asthma but Dispensable for Their Differentiation and Function |
| title_fullStr | PARP-1 Is Critical for Recruitment of Dendritic Cells to the Lung in a Mouse Model of Asthma but Dispensable for Their Differentiation and Function |
| title_full_unstemmed | PARP-1 Is Critical for Recruitment of Dendritic Cells to the Lung in a Mouse Model of Asthma but Dispensable for Their Differentiation and Function |
| title_short | PARP-1 Is Critical for Recruitment of Dendritic Cells to the Lung in a Mouse Model of Asthma but Dispensable for Their Differentiation and Function |
| title_sort | parp 1 is critical for recruitment of dendritic cells to the lung in a mouse model of asthma but dispensable for their differentiation and function |
| url | http://dx.doi.org/10.1155/2019/1656484 |
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