Regulation of Discrete Functional Responses by Syk and Src Family Tyrosine Kinases in Human Neutrophils
Neutrophils play a critical role in innate immunity and also influence adaptive immune responses. This occurs in good part through their production of inflammatory and immunomodulatory cytokines, in conjunction with their prolonged survival at inflamed foci. While a picture of the signaling machiner...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2017/4347121 |
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| author | Thornin Ear Olga Tatsiy Frédérick L. Allard Patrick P. McDonald |
| author_facet | Thornin Ear Olga Tatsiy Frédérick L. Allard Patrick P. McDonald |
| author_sort | Thornin Ear |
| collection | DOAJ |
| description | Neutrophils play a critical role in innate immunity and also influence adaptive immune responses. This occurs in good part through their production of inflammatory and immunomodulatory cytokines, in conjunction with their prolonged survival at inflamed foci. While a picture of the signaling machinery underlying these neutrophil responses is now emerging, much remains to be uncovered. In this study, we report that neutrophils constitutively express various Src family isoforms (STKs), as well as Syk, and that inhibition of these protein tyrosine kinases selectively hinders inflammatory cytokine generation by acting posttranscriptionally. Accordingly, STK or Syk inhibition decreases the phosphorylation of signaling intermediates (e.g., eIF-4E, S6K, and MNK1) involved in translational control. By contrast, delayed apoptosis appears to be independent of either STKs or Syk. Our data therefore significantly extend our understanding of which neutrophil responses are governed by STKs and Syk and pinpoint some signaling intermediates that are likely involved. In view of the foremost role of neutrophils in several chronic inflammatory conditions, our findings identify potential molecular targets that could be exploited for future therapeutic intervention. |
| format | Article |
| id | doaj-art-004e973225634130b4f34900d130e40e |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-004e973225634130b4f34900d130e40e2025-08-20T03:55:23ZengWileyJournal of Immunology Research2314-88612314-71562017-01-01201710.1155/2017/43471214347121Regulation of Discrete Functional Responses by Syk and Src Family Tyrosine Kinases in Human NeutrophilsThornin Ear0Olga Tatsiy1Frédérick L. Allard2Patrick P. McDonald3Pulmonary Division, Faculty of Medicine, Université de Sherbrooke and CRCHUS, Sherbrooke, QC, CanadaPulmonary Division, Faculty of Medicine, Université de Sherbrooke and CRCHUS, Sherbrooke, QC, CanadaPulmonary Division, Faculty of Medicine, Université de Sherbrooke and CRCHUS, Sherbrooke, QC, CanadaPulmonary Division, Faculty of Medicine, Université de Sherbrooke and CRCHUS, Sherbrooke, QC, CanadaNeutrophils play a critical role in innate immunity and also influence adaptive immune responses. This occurs in good part through their production of inflammatory and immunomodulatory cytokines, in conjunction with their prolonged survival at inflamed foci. While a picture of the signaling machinery underlying these neutrophil responses is now emerging, much remains to be uncovered. In this study, we report that neutrophils constitutively express various Src family isoforms (STKs), as well as Syk, and that inhibition of these protein tyrosine kinases selectively hinders inflammatory cytokine generation by acting posttranscriptionally. Accordingly, STK or Syk inhibition decreases the phosphorylation of signaling intermediates (e.g., eIF-4E, S6K, and MNK1) involved in translational control. By contrast, delayed apoptosis appears to be independent of either STKs or Syk. Our data therefore significantly extend our understanding of which neutrophil responses are governed by STKs and Syk and pinpoint some signaling intermediates that are likely involved. In view of the foremost role of neutrophils in several chronic inflammatory conditions, our findings identify potential molecular targets that could be exploited for future therapeutic intervention.http://dx.doi.org/10.1155/2017/4347121 |
| spellingShingle | Thornin Ear Olga Tatsiy Frédérick L. Allard Patrick P. McDonald Regulation of Discrete Functional Responses by Syk and Src Family Tyrosine Kinases in Human Neutrophils Journal of Immunology Research |
| title | Regulation of Discrete Functional Responses by Syk and Src Family Tyrosine Kinases in Human Neutrophils |
| title_full | Regulation of Discrete Functional Responses by Syk and Src Family Tyrosine Kinases in Human Neutrophils |
| title_fullStr | Regulation of Discrete Functional Responses by Syk and Src Family Tyrosine Kinases in Human Neutrophils |
| title_full_unstemmed | Regulation of Discrete Functional Responses by Syk and Src Family Tyrosine Kinases in Human Neutrophils |
| title_short | Regulation of Discrete Functional Responses by Syk and Src Family Tyrosine Kinases in Human Neutrophils |
| title_sort | regulation of discrete functional responses by syk and src family tyrosine kinases in human neutrophils |
| url | http://dx.doi.org/10.1155/2017/4347121 |
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