| Autor: |
Agliano F; Department of Immunology, University of Connecticut Health Center, Farmington, CT, USA., Karlinsey KS; Department of Immunology, University of Connecticut Health Center, Farmington, CT, USA., Ragazzi M; Department of Immunology, University of Connecticut Health Center, Farmington, CT, USA., Ménoret A; Department of Immunology, University of Connecticut Health Center, Farmington, CT, USA. menoret@uchc.edu.; Institute for Systems Genomics, UConn Health, Farmington, CT, USA. menoret@uchc.edu., Vella AT; Department of Immunology, University of Connecticut Health Center, Farmington, CT, USA. vella@uchc.edu. |
| Jazyk: |
angličtina |
| Zdroj: |
Scientific reports [Sci Rep] 2020 Jul 21; Vol. 10 (1), pp. 12100. Date of Electronic Publication: 2020 Jul 21. |
| DOI: |
10.1038/s41598-020-68985-1 |
| Abstrakt: |
Sterile stimuli can trigger inflammatory responses, and in some cases can lead to a variety of acute or chronic diseases. In this study, we hypothesize that a benzimidazole inhibitor may be used as a therapeutic in the treatment of sterile inflammation. In vitro, this inhibitor blocks TLR signalling and inflammatory responses. The benzimidazole inhibitor does not prevent mouse macrophage activation after stimulation with 2,6,10,14-tetramethylpentadecane (TMPD, also known as pristane), a hydrocarbon oil that mimics features of sterile inflammation when injected in vivo. However, C57BL/6J female mice treated with the benzimidazole inhibitor exhibited a significant reduction of pristane-dependent induction of splenocyte number and weight. Conversely, no significant difference was observed in males. Using mass spectrometry, we found that the urine of pristane-injected mice contained increased levels of putative markers for several inflammatory diseases, which were reduced by the benzimidazole inhibitor. To study the mechanism, we showed that pristane-injected mice had increased cell free DNA in serum, which was not impacted by inhibitor treatment. However, chemokine release (e.g. MCP-1, RANTES and TARC) was significantly reduced in inhibitor-treated mice. Thus, the benzimidazole inhibitor might be used as a new drug to block the recruitment of immune cells during sterile inflammatory diseases in humans. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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