Mast Cell-Mediated Inhibition of Abdominal Neutrophil Inflammation by a PEGylated TLR7 Ligand
Although the mechanisms for sustained chemokine gradients and recurring cell infiltration in sterile peritonitis have not been elucidated, toll-like receptors (TLRs) have been implicated. To abate the deleterious recruitment of neutrophils in sterile inflammation, we repeatedly administered a TLR7 l...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2012/262394 |
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| _version_ | 1832559454068932608 |
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| author | Tomoko Hayashi Shiyin Yao Brian Crain Michael Chan Howard B. Cottam Fitzgerald Lao Dennis A. Carson Maripat Corr |
| author_facet | Tomoko Hayashi Shiyin Yao Brian Crain Michael Chan Howard B. Cottam Fitzgerald Lao Dennis A. Carson Maripat Corr |
| author_sort | Tomoko Hayashi |
| collection | DOAJ |
| description | Although the mechanisms for sustained chemokine gradients and recurring cell infiltration in sterile peritonitis have not been elucidated, toll-like receptors (TLRs) have been implicated. To abate the deleterious recruitment of neutrophils in sterile inflammation, we repeatedly administered a TLR7 ligand that hyposensitized to TLR7 and receptors that converged on the MyD88-signaling intermediary and reduced cellular infiltration in murine autoimmune models of multiple sclerosis and arthritis. To reduce potential adverse effects, a polyethylene glycol polymer was covalently attached to the parent compound (Tolerimod1). The proinflammatory potency of Tolerimod1 was 10-fold less than the unconjugated TLR7 ligand, and Tolerimod1 reduced neutrophil recruitment in chemically induced peritonitis and colitis. The effects of Tolerimod1 were mediated by the radioresistant cells in radiation chimeric mice and by mast cells in reconstituted mast cell-deficient mice (KitW-sh). Although the Tolerimod1 had weak proinflammatory agonist activity, it effectively reduced neutrophil recruitment in sterile peritoneal inflammation. |
| format | Article |
| id | doaj-art-dd5fea98f935404ba6f705a28f0c9036 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-dd5fea98f935404ba6f705a28f0c90362025-02-03T01:30:09ZengWileyMediators of Inflammation0962-93511466-18612012-01-01201210.1155/2012/262394262394Mast Cell-Mediated Inhibition of Abdominal Neutrophil Inflammation by a PEGylated TLR7 LigandTomoko Hayashi0Shiyin Yao1Brian Crain2Michael Chan3Howard B. Cottam4Fitzgerald Lao5Dennis A. Carson6Maripat Corr7Moores Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, San Diego, CA 92093-0820, USAMoores Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, San Diego, CA 92093-0820, USAMoores Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, San Diego, CA 92093-0820, USAMoores Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, San Diego, CA 92093-0820, USAMoores Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, San Diego, CA 92093-0820, USAMoores Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, San Diego, CA 92093-0820, USAMoores Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, San Diego, CA 92093-0820, USADepartment of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, San Diego, CA 92093-0663, USAAlthough the mechanisms for sustained chemokine gradients and recurring cell infiltration in sterile peritonitis have not been elucidated, toll-like receptors (TLRs) have been implicated. To abate the deleterious recruitment of neutrophils in sterile inflammation, we repeatedly administered a TLR7 ligand that hyposensitized to TLR7 and receptors that converged on the MyD88-signaling intermediary and reduced cellular infiltration in murine autoimmune models of multiple sclerosis and arthritis. To reduce potential adverse effects, a polyethylene glycol polymer was covalently attached to the parent compound (Tolerimod1). The proinflammatory potency of Tolerimod1 was 10-fold less than the unconjugated TLR7 ligand, and Tolerimod1 reduced neutrophil recruitment in chemically induced peritonitis and colitis. The effects of Tolerimod1 were mediated by the radioresistant cells in radiation chimeric mice and by mast cells in reconstituted mast cell-deficient mice (KitW-sh). Although the Tolerimod1 had weak proinflammatory agonist activity, it effectively reduced neutrophil recruitment in sterile peritoneal inflammation.http://dx.doi.org/10.1155/2012/262394 |
| spellingShingle | Tomoko Hayashi Shiyin Yao Brian Crain Michael Chan Howard B. Cottam Fitzgerald Lao Dennis A. Carson Maripat Corr Mast Cell-Mediated Inhibition of Abdominal Neutrophil Inflammation by a PEGylated TLR7 Ligand Mediators of Inflammation |
| title | Mast Cell-Mediated Inhibition of Abdominal Neutrophil Inflammation by a PEGylated TLR7 Ligand |
| title_full | Mast Cell-Mediated Inhibition of Abdominal Neutrophil Inflammation by a PEGylated TLR7 Ligand |
| title_fullStr | Mast Cell-Mediated Inhibition of Abdominal Neutrophil Inflammation by a PEGylated TLR7 Ligand |
| title_full_unstemmed | Mast Cell-Mediated Inhibition of Abdominal Neutrophil Inflammation by a PEGylated TLR7 Ligand |
| title_short | Mast Cell-Mediated Inhibition of Abdominal Neutrophil Inflammation by a PEGylated TLR7 Ligand |
| title_sort | mast cell mediated inhibition of abdominal neutrophil inflammation by a pegylated tlr7 ligand |
| url | http://dx.doi.org/10.1155/2012/262394 |
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