scholarly journals The Role of Cutibacterium acnes in Intervertebral Disc Inflammation

Biomedicines ◽  
2020 ◽  
Vol 8 (7) ◽  
pp. 186 ◽  
Author(s):  
Bettina Schmid ◽  
Oliver Hausmann ◽  
Wolfgang Hitzl ◽  
Yvonne Achermann ◽  
Karin Wuertz-Kozak
Keyword(s):  
Intervertebral Disc ◽  
Toll Like Receptor ◽  
Cutibacterium Acnes ◽  
Sparstolonin B ◽  
Inflammatory Processes ◽  
Oxide Synthase ◽  
Aerobic And Anaerobic ◽  
Inducible Nitric Oxide

Recently, the role of infection of the intervertebral disc (IVD) with Cutibacterium acnes (C. acnes) as a contributor to disc-related low back pain (LBP) has been discussed. The aim of this study was to investigate whether and how C. acnes contributes to the inflammatory processes during IVD disease. The prevalence of C. acnes infection in human IVD tissue was determined by aerobic and anaerobic culture. Thereafter, primary human IVD cells were infected with a reference and a clinical C. acnes strain and analyzed for pro-inflammatory markers (gene/protein level). In a subsequent experiment, the involvement of the Toll-like receptor (TLR) pathway was investigated by co-treatment with sparstolonin B, a TLR2/4 inhibitor. We detected C. acnes in 10% of IVD biopsies (with either herniation or degeneration). Stimulating IVD cells with both C. acnes strains strongly and significantly upregulated expression of Interleukin (IL)-1β, IL-6, IL-8, and inducible nitric oxide synthase (iNOS). IL-6, cyclooxygenase (COX)-2, and iNOS expression was reduced upon TLR2/4 inhibition in 3 out of 5 donors, whereby responders and non-responders could not be differentiated by their basal TLR2 or TLR4 expression levels. We demonstrate that exposure of IVD cells to C. acnes induces an inflammatory response that may contribute to the development of discogenic LBP by involving TLR2/4 activation, yet only in a subgroup of patients. Whether the same response will be observed in vivo and where lower inoculums are present remains to be proven in future studies.

Vasculoprotective Role of Inducible Nitric Oxide Synthase at Inflammatory Coronary Lesions Induced by Chronic Treatment With Interleukin-1β in Pigs in Vivo

Circulation ◽  
1997 ◽  
Vol 96 (9) ◽  
pp. 3104-3111 ◽  
Author(s):  
Yoshihiro Fukumoto ◽  
Hiroaki Shimokawa ◽  
Toshiyuki Kozai ◽  
Toshiaki Kadokami ◽  
Kouichi Kuwata ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Chronic Treatment ◽  
Interleukin 1Β ◽  
Coronary Lesions ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The gastric mucus layers: constituents and regulation of accumulation

2008 ◽  
Vol 295 (4) ◽  
pp. G806-G812 ◽  
Author(s):  
Mia Phillipson ◽  
Malin E. V. Johansson ◽  
Johanna Henriksnäs ◽  
Joel Petersson ◽  
Sandra J. Gendler ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Accumulation Rate ◽  
Mucus Layer ◽  
Gastric Mucus ◽  
Oxide Synthase ◽  
Deficient Mice ◽  
Individual Regulation ◽  
Inducible Nitric Oxide

The mucus layer continuously covering the gastric mucosa consists of a loosely adherent layer that can be easily removed by suction, leaving a firmly adherent mucus layer attached to the epithelium. These two layers exhibit different gastroprotective roles; therefore, individual regulation of thickness and mucin composition were studied. Mucus thickness was measured in vivo with micropipettes in anesthetized mice [isoflurane; C57BL/6, Muc1−/−, inducible nitric oxide synthase (iNOS)−/−, and neuronal NOS (nNOS)−/−] and rats (inactin) after surgical exposure of the gastric mucosa. The two mucus layers covering the gastric mucosa were differently regulated. Luminal administration of PGE2increased the thickness of both layers, whereas luminal NO stimulated only firmly adherent mucus accumulation. A new gastroprotective role for iNOS was indicated since iNOS-deficient mice had thinner firmly adherent mucus layers and a lower mucus accumulation rate, whereas nNOS did not appear to be involved in mucus secretion. Downregulation of gastric mucus accumulation was observed in Muc1−/− mice. Both the firmly and loosely adherent mucus layers consisted of Muc5ac mucins. In conclusion, this study showed that, even though both the two mucus layers covering the gastric mucosa consist of Muc5ac, they are differently regulated by luminal PGE2and NO. A new gastroprotective role for iNOS was indicated since iNOS−/− mice had a thinner firmly adherent mucus layer. In addition, a regulatory role of Muc1 was demonstrated since downregulation of gastric mucus accumulation was observed in Muc1−/− mice.

Specific Role of Neutrophil Inducible Nitric Oxide Synthase in Murine Sepsis-Induced Lung Injury In Vivo

Shock ◽  
2012 ◽  
Vol 37 (5) ◽  
pp. 539-547 ◽  
Author(s):  
Lefeng Wang ◽  
Ravi Taneja ◽  
Habib Moshref Razavi ◽  
Cedrin Law ◽  
Christopher Gillis ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Lung Injury ◽  
Inducible Nitric Oxide Synthase ◽  
Specific Role ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The Signaling Pathways in Nitric Oxide Production by Neutrophils Exposed to N-nitrosodimethylamine

2018 ◽  
Vol 16 (2) ◽  
pp. 194-199
Author(s):  
Wioletta Ratajczak-Wrona ◽  
Ewa Jablonska
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Polymorphonuclear Neutrophils ◽  
Microbial Pathogens ◽  
Human Neutrophils ◽  
No Production ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Background: Polymorphonuclear neutrophils (PMNs) play a crucial role in the innate immune system’s response to microbial pathogens through the release of reactive nitrogen species, including Nitric Oxide (NO). </P><P> Methods: In neutrophils, NO is produced by the inducible Nitric Oxide Synthase (iNOS), which is regulated by various signaling pathways and transcription factors. N-nitrosodimethylamine (NDMA), a potential human carcinogen, affects immune cells. NDMA plays a major part in the growing incidence of cancers. Thanks to the increasing knowledge on the toxicological role of NDMA, the environmental factors that condition the exposure to this compound, especially its precursors- nitrates arouse wide concern. Results: In this article, we present a detailed summary of the molecular mechanisms of NDMA’s effect on the iNOS-dependent NO production in human neutrophils. Conclusion: This research contributes to a more complete understanding of the mechanisms that explain the changes that occur during nonspecific cellular responses to NDMA toxicity.

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