TLR2 Derangements Likely Play a Significant Role in the Inflammatory Response and Thrombosis in Patients with Ph(−) Classical Myeloproliferative Neoplasm
We investigated the role of toll-like receptors (TLRs) in inflammatory pathways in Philadelphia chromosome-negative myeloproliferative neoplasms (Ph(−)MPNs). TLR2 expression was increased in ET, PV, and MPN (grouped as (PV + (ET) + MF)), whereas TLR4 was elevated only in MPN. TLR3, 7, and 9 were not...
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Wiley
2024-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2024/1827127 |
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| author | Jen Chin Wang Guanfang Shi Chi Chen Ching Wong Vladimir Gotlieb Gardith Joseph Kiron V Nair Lakshmi Boyapati Enayati Ladan James T. Symanowski Lishi Sun |
| author_facet | Jen Chin Wang Guanfang Shi Chi Chen Ching Wong Vladimir Gotlieb Gardith Joseph Kiron V Nair Lakshmi Boyapati Enayati Ladan James T. Symanowski Lishi Sun |
| author_sort | Jen Chin Wang |
| collection | DOAJ |
| description | We investigated the role of toll-like receptors (TLRs) in inflammatory pathways in Philadelphia chromosome-negative myeloproliferative neoplasms (Ph(−)MPNs). TLR2 expression was increased in ET, PV, and MPN (grouped as (PV + (ET) + MF)), whereas TLR4 was elevated only in MPN. TLR3, 7, and 9 were not elevated. Cultured monocyte-derived dendritic cells and plasma assays in TLR2-elevated patients were found to secrete more cytokines than those from TLR2-normal patients. These facts suggest that TLR2 is the major inflammatory pathways in MPN. We also measured S100A9 and reactive oxygen species (ROS), revealing increased S100A9 in PV, MF, and MPN, while ROS were only increased in MF. These data suggests that MPNs initially involve TLR2, with minor contributions from TLR4, and with S100A9, leading to ROS formation, JAK2 mutation, and progression to MF or leukemia. Furthermore, patients with JAK2 mutations or leukocytosis exhibited higher TLR2 expression. In leukocyte–platelet interactions, cells from MPN patients displayed a stronger response to a TLR2 agonist than TLR4 agonist. A TLR2 inhibitor (but not a TLR4 inhibitor) attenuated this response. Thrombosis incidence was higher in TLR2-elevated patients (29%) than in TLR2-normal patients (19%). These findings suggest that TLR2 likely contributes to thrombosis in MPN. |
| format | Article |
| id | doaj-art-0bbd7efcd772411a889e3e97d678ed93 |
| institution | DOAJ |
| issn | 1466-1861 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-0bbd7efcd772411a889e3e97d678ed932025-08-20T02:43:10ZengWileyMediators of Inflammation1466-18612024-01-01202410.1155/2024/1827127TLR2 Derangements Likely Play a Significant Role in the Inflammatory Response and Thrombosis in Patients with Ph(−) Classical Myeloproliferative NeoplasmJen Chin Wang0Guanfang Shi1Chi Chen2Ching Wong3Vladimir Gotlieb4Gardith Joseph5Kiron V Nair6Lakshmi Boyapati7Enayati Ladan8James T. Symanowski9Lishi Sun10Division of Hematology/OncologyDivision of Hematology/OncologyDivision of Hematology/OncologyDivision of Hematology/OncologyDivision of Hematology/OncologyDivision of Hematology/OncologyDivision of Hematology/OncologyDivision of Hematology/OncologyDivision of Hematology/OncologyDepartment of Biostatistics and Data SciencesDivision of Hematology/OncologyWe investigated the role of toll-like receptors (TLRs) in inflammatory pathways in Philadelphia chromosome-negative myeloproliferative neoplasms (Ph(−)MPNs). TLR2 expression was increased in ET, PV, and MPN (grouped as (PV + (ET) + MF)), whereas TLR4 was elevated only in MPN. TLR3, 7, and 9 were not elevated. Cultured monocyte-derived dendritic cells and plasma assays in TLR2-elevated patients were found to secrete more cytokines than those from TLR2-normal patients. These facts suggest that TLR2 is the major inflammatory pathways in MPN. We also measured S100A9 and reactive oxygen species (ROS), revealing increased S100A9 in PV, MF, and MPN, while ROS were only increased in MF. These data suggests that MPNs initially involve TLR2, with minor contributions from TLR4, and with S100A9, leading to ROS formation, JAK2 mutation, and progression to MF or leukemia. Furthermore, patients with JAK2 mutations or leukocytosis exhibited higher TLR2 expression. In leukocyte–platelet interactions, cells from MPN patients displayed a stronger response to a TLR2 agonist than TLR4 agonist. A TLR2 inhibitor (but not a TLR4 inhibitor) attenuated this response. Thrombosis incidence was higher in TLR2-elevated patients (29%) than in TLR2-normal patients (19%). These findings suggest that TLR2 likely contributes to thrombosis in MPN.http://dx.doi.org/10.1155/2024/1827127 |
| spellingShingle | Jen Chin Wang Guanfang Shi Chi Chen Ching Wong Vladimir Gotlieb Gardith Joseph Kiron V Nair Lakshmi Boyapati Enayati Ladan James T. Symanowski Lishi Sun TLR2 Derangements Likely Play a Significant Role in the Inflammatory Response and Thrombosis in Patients with Ph(−) Classical Myeloproliferative Neoplasm Mediators of Inflammation |
| title | TLR2 Derangements Likely Play a Significant Role in the Inflammatory Response and Thrombosis in Patients with Ph(−) Classical Myeloproliferative Neoplasm |
| title_full | TLR2 Derangements Likely Play a Significant Role in the Inflammatory Response and Thrombosis in Patients with Ph(−) Classical Myeloproliferative Neoplasm |
| title_fullStr | TLR2 Derangements Likely Play a Significant Role in the Inflammatory Response and Thrombosis in Patients with Ph(−) Classical Myeloproliferative Neoplasm |
| title_full_unstemmed | TLR2 Derangements Likely Play a Significant Role in the Inflammatory Response and Thrombosis in Patients with Ph(−) Classical Myeloproliferative Neoplasm |
| title_short | TLR2 Derangements Likely Play a Significant Role in the Inflammatory Response and Thrombosis in Patients with Ph(−) Classical Myeloproliferative Neoplasm |
| title_sort | tlr2 derangements likely play a significant role in the inflammatory response and thrombosis in patients with ph classical myeloproliferative neoplasm |
| url | http://dx.doi.org/10.1155/2024/1827127 |
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