Signaling through cannabinoid receptor 2 suppresses murine dendritic cell migration by inhibiting matrix metalloproteinase 9 expression
| Autor: | Doina Ganea, Sabina Adhikary, Virginia Kocieda, Jui-Hung Yen, Ronald F. Tuma |
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| Rok vydání: | 2012 |
| Předmět: |
MAPK/ERK pathway
Leukocyte migration Blotting Western Immunology Enzyme-Linked Immunosorbent Assay Inflammation Biology Real-Time Polymerase Chain Reaction Biochemistry Receptor Cannabinoid CB2 Mice Immune system Cell Movement Cannabinoid receptor type 2 medicine Animals Dendritic cell migration Immunobiology Oligonucleotide Array Sequence Analysis Mice Knockout Migration Assay Reverse Transcriptase Polymerase Chain Reaction Dendritic Cells Cell Biology Hematology Flow Cytometry Cell biology Mice Inbred C57BL Chemotaxis Leukocyte Matrix Metalloproteinase 9 Signal transduction medicine.symptom Signal Transduction |
| Zdroj: | Blood. 120:3741-3749 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2012-06-435362 |
| Popis: | Administration of cannabinoid receptor 2 (CB2R) agonists in inflammatory and autoimmune disease and CNS injury models results in significant attenuation of clinical disease, and reduction of inflammatory mediators. Previous studies reported that CB2R signaling also reduces leukocyte migration. Migration of dendritic cells (DCs) to various sites is required for their activation and for the initiation of adaptive immune responses. Here, we report for the first time that CB2R signaling affects DC migration in vitro and in vivo, primarily through the inhibition of matrix metalloproteinase 9 (MMP-9) expression. Reduced MMP-9 production by DCs results in decreased migration to draining lymph nodes in vivo and in vitro in the matrigel migration assay. The effect on Mmp-9 expression is mediated through CB2R, resulting in reduction in cAMP levels, subsequent decrease in ERK activation, and reduced binding of c-Fos and c-Jun to Mmp-9 promoter activator protein 1 sites. We postulate that, by dampening production of MMP-9 and subsequent MMP-9–dependent DC migration, cannabinoids contribute to resolve acute inflammation and to reestablish homeostasis. Selective CB2R agonists might be valuable future therapeutic agents for the treatment of chronic inflammatory conditions by targeting activated immune cells, including DCs. |
| Databáze: | OpenAIRE |
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