Cannabinoid signalling in TNF-α induced IL-8 release
| Autor: | Anwar R. Baydoun, A Molleman, Cliff J. Whelan, Maria E. Mormina, Shori Thakur |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
Leupeptins Morpholines medicine.medical_treatment Blotting Western Enzyme-Linked Immunosorbent Assay Inflammation Cysteine Proteinase Inhibitors Naphthalenes Pharmacology Internal medicine medicine Cannabinoid receptor type 2 Humans Electrophoretic mobility shift assay Cycloheximide Receptors Cannabinoid Cannabinoid Receptor Agonists Protein Synthesis Inhibitors Dose-Response Relationship Drug Cannabinoids Tumor Necrosis Factor-alpha Chemistry Interleukin-8 NF-kappa B NFKB1 Benzoxazines Up-Regulation Endocrinology Cytokine Dactinomycin I-kappa B Proteins Tumor necrosis factor alpha Cannabinoid medicine.symptom Signal transduction HT29 Cells Signal Transduction |
| Zdroj: | European Journal of Pharmacology. 540:183-190 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2006.04.015 |
| Popis: | The molecular events mediating the immunomodulatory properties of cannabinoids have remained largely unresolved. We have therefore investigated the molecular mechanism(s) through which R-(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl] pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-napthanlenyl) methanone (WIN55212-2) modulate production of interleukin-8 (IL-8) in HT-29 cells. Release of IL-8 induced by tumor necrosis factor-alpha (TNF-alpha) was determined by enzyme-linked immunosorbent assay (ELISA). Changes in expression of inhibitory kappa B (IkappaB) were monitored by Western blotting and activation of nuclear factor-kappa B (NF-kappaB) was determined in electrophoretic mobility shift assay (EMSAs). TNF-alpha induced release of IL-8 was inhibited by WIN55212-2 which also blocked the degradation of IkappaB-alpha and activation of NF-kappaB induced by TNF-alpha. These data provide strong evidence that WIN55212-2 may modulate IL-8 release by negatively regulating the signaling cascade leading to the activation of NF-kappaB. These findings highlight a potential mechanism for the immunomodulatory properties of cannabinoids and contribute towards acquiring a clear understanding of the role of cannabinoids in inflammation. |
| Databáze: | OpenAIRE |
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