CDKI-73 is a Novel Pharmacological Inhibitor of Rab11 Cargo Delivery and Innate Immune Secretion
| Autor: | Stavros Selemidis, Alexandra Sorvina, Douglas A. Brooks, Emma J. Parkinson-Lawrence, Shudong Wang, David J. Sharkey, Tetyana Shandala |
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| Přispěvatelé: | Sorvina, Alexandra, Shandala, Tetyana, Wang, Shudong, Sharkey, David J, Parkinson-Lawrence, Emma, Selemidis, Stavros, Brooks, Douglas A |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
THP-1 Cells
Endosome Fat Body Cell Antimicrobial peptides Inflammation Membrane Fusion Article 03 medical and health sciences 0302 clinical medicine medicine TNFα Animals Humans Secretion antimicrobial peptide Drosomycin Interleukin 6 lcsh:QH301-705.5 CDKI-73 030304 developmental biology Sulfonamides 0303 health sciences IL-6 Innate immune system biology Macrophages General Medicine Immunity Innate 3. Good health Cell biology Protein Transport Pyrimidines medicine.anatomical_structure Drosophila lcsh:Biology (General) rab GTP-Binding Proteins endosomes 030220 oncology & carcinogenesis Rab11 biology.protein Cytokines Tumor necrosis factor alpha Inflammation Mediators medicine.symptom TNF alpha |
| Zdroj: | Cells Volume 9 Issue 2 Cells, Vol 9, Iss 2, p 372 (2020) |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells9020372 |
| Popis: | Innate immunity is critical for host defence against pathogen and environmental challenge and this involves the production and secretion of immune mediators, such as antimicrobial peptides and pro-inflammatory cytokines. However, when dysregulated, innate immunity can contribute to multifactorial diseases, including inflammatory rheumatic disorders, type 2 diabetes, cancer, neurodegenerative and cardiovascular diseases and even septic shock. During an innate immune response, antimicrobial peptides and cytokines are trafficked via Rab11 multivesicular endosomes, and then sorted into Rab11 vesicles for traffic to the plasma membrane and secretion. In this study, a cyclin-dependent kinase inhibitor CDKI-73 was used to determine its effect on the innate immune response, based on previously identified targets for this compound. Our results showed that CDKI-73 inhibited the delivery of Rab11 vesicles to the plasma membrane, resulting in the accumulation of large multivesicular Rab11 endosomes near the cell periphery. In addition to the effect on endosome delivery, CDKI-73 down-regulated the amount of innate immune cargo, including the antimicrobial peptide Drosomycin and pro-inflammatory cytokines interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF&alpha ). We concluded that CDKI-73 has the potential to regulate the delivery and secretion of certain innate immune cargo, which could be used to control inflammation. |
| Databáze: | OpenAIRE |
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