fMet-Leu-Phe Stimulates Proinflammatory Cytokine Gene Expression in Human Peripheral Blood Monocytes: The Role of Phosphatidylinositol 3-Kinase
| Autor: | Bruce L. Zuraw, Ling-Yu Chen, Charles G. Cochrane, Zhixing K. Pan |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Transcriptional Activation
Immunology Mutant Biology Peripheral blood mononuclear cell Monocytes Proinflammatory cytokine Wortmannin Phosphatidylinositol 3-Kinases chemistry.chemical_compound Gene expression Humans Immunology and Allergy LY294002 Phosphatidylinositol Phosphoinositide-3 Kinase Inhibitors Kinase NF-kappa B hemic and immune systems Macrophage Activation Cell biology Enzyme Activation N-Formylmethionine Leucyl-Phenylalanine Gene Expression Regulation chemistry Cytokines lipids (amino acids peptides and proteins) Inflammation Mediators Interleukin-1 |
| Zdroj: | The Journal of Immunology. 164:404-411 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.164.1.404 |
| Popis: | The fMLP-stimulated release of proinflammatory cytokines such as IL-1 by human peripheral blood monocytes is an important component of the inflammatory process. The signaling mechanisms used by fMLP to stimulate the release of cytokines are still incompletely understood. We previously demonstrated that fMLP-stimulated NF-κB activation in PBMC and now we present evidence that the lipid products of phosphatidylinositol 3-kinase (PI 3-kinase) are required for fMLP-stimulated activation of NF-κB. Pretreatment with the PI 3-kinase inhibitors, wortmannin and LY294002, effectively blocked fMLP-induced IL-1β gene expression as well as NF-κB activation. Transient transfection of THP1 cells with a dominant-negative mutant of the PI 3-kinase p85 subunit also abrogated fMLP-induced κB activity. These results suggest a potential role of fMLP in the transcription of proinflammatory cytokines and provide the first evidence that such regulation may occur through PI 3-kinase activity. |
| Databáze: | OpenAIRE |
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