The p110α and p110β Isoforms of Class I Phosphatidylinositol 3-Kinase Are Involved in Toll-Like Receptor 5 Signaling in Epithelial Cells
Background. Bacterial flagellin triggers inflammation in mammalian cells via Toll-like receptor (TLR) 5. Release of the chemokine IL-8 in response to flagellin involves NF-κB, p38 MAP kinase, and phosphatidylinositol 3-kinase (PI3K). However, PI3K has been reported to be either pro- or anti-inflamma...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2010-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2010/652098 |
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| author | Sabine M. Ivison Mohammed A. S. Khan Nicholas R. Graham Leila A. Shobab Yu Yao Arnawaz Kifayet Laura M. Sly Theodore S. Steiner |
| author_facet | Sabine M. Ivison Mohammed A. S. Khan Nicholas R. Graham Leila A. Shobab Yu Yao Arnawaz Kifayet Laura M. Sly Theodore S. Steiner |
| author_sort | Sabine M. Ivison |
| collection | DOAJ |
| description | Background. Bacterial flagellin triggers inflammation in mammalian cells via Toll-like receptor (TLR) 5. Release of the chemokine IL-8 in response to flagellin involves NF-κB, p38 MAP kinase, and phosphatidylinositol 3-kinase (PI3K). However, PI3K has been reported to be either pro- or anti-inflammatory in different model systems. We hypothesized that this could be due to different activities of the p110α and β isoforms of PI3K. Results. PI3K and Akt were rapidly activated in Caco-2 colon carcinoma cells by flagellin. Using a plasmid-based shRNA delivery system and novel p110 isoform-specific inhibitors, we found that flagellin-induced IL-8 production was dependent on both p110α and p110β. However in the mouse, inhibition of p110β but not p110α reduced the increase of serum IL-6 levels induced by intraperitoneal injection of flagellin. Conclusions. These data demonstrate that the p110α and β isoforms of class IA PI3K are both required for the proinflammatory response to flagellin. |
| format | Article |
| id | doaj-art-a76f7f4886c64651b19dc94763c256ba |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-a76f7f4886c64651b19dc94763c256ba2025-02-03T05:46:08ZengWileyMediators of Inflammation0962-93511466-18612010-01-01201010.1155/2010/652098652098The p110α and p110β Isoforms of Class I Phosphatidylinositol 3-Kinase Are Involved in Toll-Like Receptor 5 Signaling in Epithelial CellsSabine M. Ivison0Mohammed A. S. Khan1Nicholas R. Graham2Leila A. Shobab3Yu Yao4Arnawaz Kifayet5Laura M. Sly6Theodore S. Steiner7Division of Infectious Diseases, Department of Medicine, Vancouver Coastal Research Institute (VCRI), Faculty of Medicin, University of British Columbia, Rm D452 HP East, 2733 Heather St., Vancouver, BC, V5Z 3J5, CanadaDivision of Infectious Diseases, Department of Medicine, Vancouver Coastal Research Institute (VCRI), Faculty of Medicin, University of British Columbia, Rm D452 HP East, 2733 Heather St., Vancouver, BC, V5Z 3J5, CanadaDivision of Infectious Diseases, Department of Medicine, Vancouver Coastal Research Institute (VCRI), Faculty of Medicin, University of British Columbia, Rm D452 HP East, 2733 Heather St., Vancouver, BC, V5Z 3J5, CanadaDivision of Infectious Diseases, Department of Medicine, Vancouver Coastal Research Institute (VCRI), Faculty of Medicin, University of British Columbia, Rm D452 HP East, 2733 Heather St., Vancouver, BC, V5Z 3J5, CanadaDivision of Infectious Diseases, Department of Medicine, Vancouver Coastal Research Institute (VCRI), Faculty of Medicin, University of British Columbia, Rm D452 HP East, 2733 Heather St., Vancouver, BC, V5Z 3J5, CanadaDivision of Infectious Diseases, Department of Medicine, Vancouver Coastal Research Institute (VCRI), Faculty of Medicin, University of British Columbia, Rm D452 HP East, 2733 Heather St., Vancouver, BC, V5Z 3J5, CanadaChild and Family Research Institute, B.C. Children's Hospital, Vancouver, BC, V6H 3V4, CanadaDivision of Infectious Diseases, Department of Medicine, Vancouver Coastal Research Institute (VCRI), Faculty of Medicin, University of British Columbia, Rm D452 HP East, 2733 Heather St., Vancouver, BC, V5Z 3J5, CanadaBackground. Bacterial flagellin triggers inflammation in mammalian cells via Toll-like receptor (TLR) 5. Release of the chemokine IL-8 in response to flagellin involves NF-κB, p38 MAP kinase, and phosphatidylinositol 3-kinase (PI3K). However, PI3K has been reported to be either pro- or anti-inflammatory in different model systems. We hypothesized that this could be due to different activities of the p110α and β isoforms of PI3K. Results. PI3K and Akt were rapidly activated in Caco-2 colon carcinoma cells by flagellin. Using a plasmid-based shRNA delivery system and novel p110 isoform-specific inhibitors, we found that flagellin-induced IL-8 production was dependent on both p110α and p110β. However in the mouse, inhibition of p110β but not p110α reduced the increase of serum IL-6 levels induced by intraperitoneal injection of flagellin. Conclusions. These data demonstrate that the p110α and β isoforms of class IA PI3K are both required for the proinflammatory response to flagellin.http://dx.doi.org/10.1155/2010/652098 |
| spellingShingle | Sabine M. Ivison Mohammed A. S. Khan Nicholas R. Graham Leila A. Shobab Yu Yao Arnawaz Kifayet Laura M. Sly Theodore S. Steiner The p110α and p110β Isoforms of Class I Phosphatidylinositol 3-Kinase Are Involved in Toll-Like Receptor 5 Signaling in Epithelial Cells Mediators of Inflammation |
| title | The p110α and p110β Isoforms of Class I Phosphatidylinositol 3-Kinase Are Involved in
Toll-Like Receptor 5 Signaling in Epithelial Cells |
| title_full | The p110α and p110β Isoforms of Class I Phosphatidylinositol 3-Kinase Are Involved in
Toll-Like Receptor 5 Signaling in Epithelial Cells |
| title_fullStr | The p110α and p110β Isoforms of Class I Phosphatidylinositol 3-Kinase Are Involved in
Toll-Like Receptor 5 Signaling in Epithelial Cells |
| title_full_unstemmed | The p110α and p110β Isoforms of Class I Phosphatidylinositol 3-Kinase Are Involved in
Toll-Like Receptor 5 Signaling in Epithelial Cells |
| title_short | The p110α and p110β Isoforms of Class I Phosphatidylinositol 3-Kinase Are Involved in
Toll-Like Receptor 5 Signaling in Epithelial Cells |
| title_sort | p110α and p110β isoforms of class i phosphatidylinositol 3 kinase are involved in toll like receptor 5 signaling in epithelial cells |
| url | http://dx.doi.org/10.1155/2010/652098 |
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