Sirtuin6 inhibits c-triggered inflammation through TLR4 abrogation regulated by ROS and TRPV1/CGRP
| Autor: | Qin Guo, Lulu Zhang, Hongmin Li, Jin Ji, Ruohua Zhang, Jie Zhu |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
SIRT6 Calcitonin Gene-Related Peptide Blotting Western TRPV1 TRPV Cation Channels Inflammation Enzyme-Linked Immunosorbent Assay Calcitonin gene-related peptide Real-Time Polymerase Chain Reaction Biochemistry Cell Line 03 medical and health sciences Downregulation and upregulation medicine Humans Sirtuins Molecular Biology Chemistry Monocyte Cell Biology Cell biology Toll-Like Receptor 4 030104 developmental biology medicine.anatomical_structure TLR4 Tumor necrosis factor alpha medicine.symptom Reactive Oxygen Species |
| Zdroj: | Journal of cellular biochemistry. 119(11) |
| ISSN: | 1097-4644 |
| Popis: | Propionibacterium acnes induces inflammatory and plays a vital role in the formation of comedones through activation of inflammatory cells, keratinocytes, and sebocytes. Sirtuin6 (SIRT6), along with ADP-ribosyltransferase and deacetylase, has been proposed to mediate various biological functions, including inflammation. Nevertheless, no strong experimental evidence has been provided to support the effect of SIRT6 in treatment of inflammatory situation. Therefore, this study addressed the inhibitory effect of SIRT6 against P. acnes-triggered inflammation in human keratinocytes and monocyte cell lines. In our study, proinflammation capacity of P. acnes was confirmed by increased levels of various inflammatory modulators, such as interleukin (IL)-1β, IL-6, IL-12, monocyte chemoattractant protein-1, interferon-γ, and tumor necrosis facto-α, both in vivo and in vitro. P. acnes stimulation also decreased SIRT6 expression, whereas, SIRT6 overexpression successfully suppressed the production of these cytokines in P. acnes-infected cells, and therefore controlled inflammation. Furthermore, we found that challenge of P. acnes stimulated the expression of toll-like receptor 4 (TLR4) in both cell lines. Nevertheless, SIRT6 overexpression attenuated the expression of TLR4 and consequently inhibited the P. acnes-triggered phosphorylation of nuclear transcription factor-kappa B (NF-κB) subunit, p65. Moreover, deactivation of TLR4 signaling pathway by SIRT6 overexpression resulted in significant downregulation of the transient receptor potential vanilloid (TRPV) pathway, cAMP response element-binding protein (CREB)/calcitonin gene-related peptide (CGRP) signaling, and NF-κB-regulated production of reactive oxygen species. These results indicate that SIRT6 serves as a potential therapeutic target to alleviate acne inflammation. |
| Databáze: | OpenAIRE |
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