Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRs
Midkine (MK) and pleiotrophin (PTN) belong to the same family of cytokines. They have similar sequences and functions. Both have important roles in cellular proliferation, tumors, and diseases. They regulate and are expressed by some immune cells. We have recently demonstrated MK production by some...
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2023-01-01
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Online Access: | http://dx.doi.org/10.1155/2023/7944102 |
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author | Elias A. Said Sumaya Al-Dughaishi Wadha Al-Hatmi Iman Al-Reesi Mohammed S. Al-Balushi Atika Al-Bimani Juma Z. Al-Busaidi Marwa Al-Riyami Murtadha Al-Khabori Salam Al-Kindi Francesco A. Procopio Shadia Al-Sinawi Aliyaa Al-Ansari Crystal Y. Koh Khalid Al-Naamani Ali A. Al-Jabri |
author_facet | Elias A. Said Sumaya Al-Dughaishi Wadha Al-Hatmi Iman Al-Reesi Mohammed S. Al-Balushi Atika Al-Bimani Juma Z. Al-Busaidi Marwa Al-Riyami Murtadha Al-Khabori Salam Al-Kindi Francesco A. Procopio Shadia Al-Sinawi Aliyaa Al-Ansari Crystal Y. Koh Khalid Al-Naamani Ali A. Al-Jabri |
author_sort | Elias A. Said |
collection | DOAJ |
description | Midkine (MK) and pleiotrophin (PTN) belong to the same family of cytokines. They have similar sequences and functions. Both have important roles in cellular proliferation, tumors, and diseases. They regulate and are expressed by some immune cells. We have recently demonstrated MK production by some human innate antigen-presenting cells (iAPCs), i.e., monocyte-derived dendritic cells (MDDCs) and macrophages stimulated through Toll-like receptor (TLR)-4, and plasmacytoid dendritic cells (pDCs) stimulated through TLR 7. While PTN production was only documented in tissue macrophages. TLRs 3, 7, 8, and 9 are nucleic acid sensing (NAS) TLRs that detect nucleic acids from cell damage and infection and induce iAPC responses. We investigated whether NAS TLRs can induce MK and PTN production by human iAPCs, namely monocytes, macrophages, MDDCs, myeloid dendritic cells (mDCs), and pDCs. Our results demonstrated for the first time that PTN is produced by all iAPCs upon TLR triggering (p<0.01). IAPCs produced more PTN than MK (p<0.01). NAS TLRs and iAPCs had differential abilities to induce the production of MK, which was induced in monocytes and pDCs by all NAS TLRs (p<0.05) and in MDDCs by TLRs 7/8 (p<0.05). TLR4 induced a stronger MK production than NAS TLRs (p≤0.05). Monocytes produced higher levels of PTN after differentiation to macrophages and MDDCs (p<0.05). The production of MK and PTN differs among iAPCs, with a higher production of PTN and a selective induction of MK production by NAS TLR. This highlights the potentially important role of iAPCs in angiogenesis, tumors, infections, and autoimmunity through the differential production of MK and PTN upon TLR triggering. |
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spelling | doaj-art-63d42028829e48bd92955fde7b1e7f602025-02-03T05:57:00ZengWileyJournal of Immunology Research2314-71562023-01-01202310.1155/2023/7944102Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRsElias A. Said0Sumaya Al-Dughaishi1Wadha Al-Hatmi2Iman Al-Reesi3Mohammed S. Al-Balushi4Atika Al-Bimani5Juma Z. Al-Busaidi6Marwa Al-Riyami7Murtadha Al-Khabori8Salam Al-Kindi9Francesco A. Procopio10Shadia Al-Sinawi11Aliyaa Al-Ansari12Crystal Y. Koh13Khalid Al-Naamani14Ali A. Al-Jabri15Department of Microbiology and ImmunologyDepartment of Microbiology and ImmunologyDepartment of Microbiology and ImmunologyDepartment of Microbiology and ImmunologyDepartment of Microbiology and ImmunologyDepartment of Microbiology and ImmunologyDepartment of Microbiology and ImmunologyDepartment of PathologyDepartment of HematologyDepartment of HematologyService of Immunology and AllergyDepartment of PathologyDepartment of BiologyDepartment of Microbiology and ImmunologyDepartment of MedicineDepartment of Microbiology and ImmunologyMidkine (MK) and pleiotrophin (PTN) belong to the same family of cytokines. They have similar sequences and functions. Both have important roles in cellular proliferation, tumors, and diseases. They regulate and are expressed by some immune cells. We have recently demonstrated MK production by some human innate antigen-presenting cells (iAPCs), i.e., monocyte-derived dendritic cells (MDDCs) and macrophages stimulated through Toll-like receptor (TLR)-4, and plasmacytoid dendritic cells (pDCs) stimulated through TLR 7. While PTN production was only documented in tissue macrophages. TLRs 3, 7, 8, and 9 are nucleic acid sensing (NAS) TLRs that detect nucleic acids from cell damage and infection and induce iAPC responses. We investigated whether NAS TLRs can induce MK and PTN production by human iAPCs, namely monocytes, macrophages, MDDCs, myeloid dendritic cells (mDCs), and pDCs. Our results demonstrated for the first time that PTN is produced by all iAPCs upon TLR triggering (p<0.01). IAPCs produced more PTN than MK (p<0.01). NAS TLRs and iAPCs had differential abilities to induce the production of MK, which was induced in monocytes and pDCs by all NAS TLRs (p<0.05) and in MDDCs by TLRs 7/8 (p<0.05). TLR4 induced a stronger MK production than NAS TLRs (p≤0.05). Monocytes produced higher levels of PTN after differentiation to macrophages and MDDCs (p<0.05). The production of MK and PTN differs among iAPCs, with a higher production of PTN and a selective induction of MK production by NAS TLR. This highlights the potentially important role of iAPCs in angiogenesis, tumors, infections, and autoimmunity through the differential production of MK and PTN upon TLR triggering.http://dx.doi.org/10.1155/2023/7944102 |
spellingShingle | Elias A. Said Sumaya Al-Dughaishi Wadha Al-Hatmi Iman Al-Reesi Mohammed S. Al-Balushi Atika Al-Bimani Juma Z. Al-Busaidi Marwa Al-Riyami Murtadha Al-Khabori Salam Al-Kindi Francesco A. Procopio Shadia Al-Sinawi Aliyaa Al-Ansari Crystal Y. Koh Khalid Al-Naamani Ali A. Al-Jabri Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRs Journal of Immunology Research |
title | Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRs |
title_full | Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRs |
title_fullStr | Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRs |
title_full_unstemmed | Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRs |
title_short | Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRs |
title_sort | differential production of midkine and pleiotrophin by innate apcs upon stimulation through nucleic acid sensing tlrs |
url | http://dx.doi.org/10.1155/2023/7944102 |
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