scholarly journals Oral Pathogenic Bacteria-Inducing Neurodegenerative Microgliosis in Human Neural Cell Platform

2021 ◽  
Vol 22 (13) ◽  
pp. 6925
Author(s):  
Tran Thi Ai Tran ◽  
You Jung Kang ◽  
Hyun-Kyoung Kim ◽  
Hyung-Ryong Kim ◽  
Hansang Cho

Porphyromonas gingivalis is a gram-negative bacterium found in the human oral cavity and is responsible for the development of chronic periodontitis as well as neurological diseases, including Alzheimer’s disease (AD). Given the significance of the roles of P. gingivalis in AD pathogenesis, it is critical to understand the underlying mechanisms of P. gingivalis-driven neuroinflammation and their contribution to neurodegeneration. Herein, we hypothesize that P. gingivalis produces secondary metabolites that may cause neurodegeneration through direct or indirect pathways mediated by microglia. To test our hypothesis, we treated human neural cells with bacterial conditioned media on our brain platforms and assessed microgliosis, astrogliosis and neurodegeneration. We found that bacteria-mediated microgliosis induced the production of nitric oxide, which causes neurodegeneration assessed with high pTau level. Our study demonstrated the elevation of detrimental protein mediators, CD86 and iNOS and the production of several pro-inflammatory markers from stimulated microglia. Through inhibition of LPS and succinate dehydrogenase in a bacterial conditioned medium, we showed a decrease in neurodegenerative microgliosis. In addition, we demonstrated the bidirectional effect of microgliosis and astrogliosis on each other exacerbating neurodegeneration. Overall, our study suggests that the mouth-brain axis may contribute to the pathogenesis of AD.

2001 ◽  
Vol 69 (10) ◽  
pp. 6119-6122 ◽  
Author(s):  
Sandra M. Merkel ◽  
Sarah Alexander ◽  
Eric Zufall ◽  
James D. Oliver ◽  
Yvette M. Huet-Hudson

ABSTRACT Little is known about the underlying mechanisms that result in a sexually dimorphic response to Vibrio vulnificus endotoxic shock. V. vulnificus is a gram-negative bacterium, considered one of the most invasive and rapidly fatal human pathogens known. However, 85% of individuals that develop endotoxic shock fromV. vulnificus are males. Using the rat, we have developed a model for V. vulnificus endotoxic shock that mimics the sexually dimorphic response in humans. Gonadectomy in females results in increased mortality, and estrogen replacement results in decreased mortality in both gonadectomized males and females. These results demonstrate that estrogen is providing protection against V. vulnificus lipopolysaccharide-induced endotoxic shock.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Qiang Zhu ◽  
Tao Tang ◽  
Haixiao Liu ◽  
Yinxue Sun ◽  
Xiaogang Wang ◽  
...  

Microglial inflammation plays an important part in the progression of multiple neurological diseases, including neurodegenerative diseases, stroke, depression, and traumatic encephalopathy. Here, we aimed to explore the role of pterostilbene (PTE) in the microglial inflammatory response and subsequent damage of cocultured neural cells and partially explain the underlying mechanisms. In the coculture system of lipopolysaccharide-activated BV-2 microglia and SH-SY5Y neuroblastoma, PTE (only given to BV-2) exhibited protection on SH-SY5Y cells, evidenced by improved SH-SY5Y morphology and viability and LDH release. It also attenuated SH-SY5Y apoptosis and oxidative stress, evidenced by TUNEL and DCFH-DA staining, as well as MDA, SOD, and GSH levels. Moreover, PTE upregulated SIRT-1 expression and suppressed acetylation of NF-κB p65 subunit in BV-2 microglia, thus decreasing the inflammatory factors, including TNF-α and IL-6. Furthermore, the effects above were reversed by SIRT-1 inhibitor EX527. These results suggest that PTE reduces the microglia-mediated inflammatory response and alleviates subsequent neuronal apoptosis and oxidative injury via increasing SIRT-1 expression and inhibiting the NF-κB signalling pathway.


Author(s):  
Andri Frediansyah ◽  
Jan Straetener ◽  
Heike Brötz-Oesterhelt ◽  
Harald Gross

AbstractA cyclic tetrapeptide, designated massiliamide, was isolated from the liquid culture of the Gram-negative bacterium Massilia albidiflava DSM 17472T. The structure was elucidated through extensive spectroscopic analysis, including HR-MS and 1D and 2D NMR experiments. The absolute configuration was determined using the Marfey´s method. Massiliamide showed potent inhibitory activity towards tyrosinase with an IC50 value of 1.15 µM and no cytotoxicity.


2021 ◽  
Vol 42 ◽  
pp. 15-22
Author(s):  
Zhaohuan Zhang ◽  
Zhenhua Huang ◽  
Jinrong Tong ◽  
Qian Wu ◽  
Yingjie Pan ◽  
...  

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Thomas V. Heidler ◽  
Karin Ernits ◽  
Agnieszka Ziolkowska ◽  
Rolf Claesson ◽  
Karina Persson

AbstractThe Gram-negative bacterium Porphyromonas gingivalis is a secondary colonizer of the oral biofilm and is involved in the onset and progression of periodontitis. Its fimbriae, of type-V, are important for attachment to other microorganisms in the biofilm and for adhesion to host cells. The fimbriae are assembled from five proteins encoded by the mfa1 operon, of which Mfa5 is one of the ancillary tip proteins. Here we report the X-ray structure of the N-terminal half of Mfa5, which reveals a von Willebrand factor domain and two IgG-like domains. One of the IgG-like domains is stabilized by an intramolecular isopeptide bond, which is the first such bond observed in a Gram-negative bacterium. These features make Mfa5 structurally more related to streptococcal adhesins than to the other P. gingivalis Mfa proteins. The structure reported here indicates that horizontal gene transfer has occurred among the bacteria within the oral biofilm.


2021 ◽  
Vol 36 (1) ◽  
pp. 372-376
Author(s):  
Andrea Petreni ◽  
Viviana De Luca ◽  
Andrea Scaloni ◽  
Alessio Nocentini ◽  
Clemente Capasso ◽  
...  

2020 ◽  
Vol 497 ◽  
pp. 108135
Author(s):  
Agnieszka Kowalczyk ◽  
Nikola Szpakowska ◽  
Wojciech Sledz ◽  
Agata Motyka-Pomagruk ◽  
Karolina Ossowska ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rosangela Montanaro ◽  
Alessio D’Addona ◽  
Andrea Izzo ◽  
Carlo Ruosi ◽  
Vincenzo Brancaleone

AbstractClodronate is a bisphosphonate agent commonly used as anti-osteoporotic drug. Throughout its use, additional anti-inflammatory and analgesic properties have been reported, although the benefits described in the literature could not solely relate to their inhibition of bone resorption. Thus, the purpose of our in vitro study is to investigate whether there are underlying mechanisms explaining the anti-inflammatory effect of clodronate and possibly involving hydrogen sulphide (H2S). Immortalised fibroblast-like synoviocyte cells (K4IM) were cultured and treated with clodronate in presence of TNF-α. Clodronate significantly modulated iNOS expression elicited by TNF-α. Inflammatory markers induced by TNF-α, including IL-1, IL-6, MCP-1 and RANTES, were also suppressed following administration of clodronate. Furthermore, the reduction in enzymatic biosynthesis of CSE-derived H2S, together with the reduction in CSE expression associated with TNF-α treatment, was reverted by clodronate, thus rescuing endogenous H2S pathway activity. Clodronate displays antinflammatory properties through the modulation of H2S pathway and cytokines levels, thus assuring the control of the inflammatory state. Although further investigation is needed to stress out how clodronate exerts its control on H2S pathway, here we showed for the first the involvement of H2S in the additive beneficial effects observed following clodronate therapy.


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