Treatment of Borrelia burgdorferi-Infected Mice with Apoptotic Cells Attenuates Lyme Arthritis via PPAR-γ.
Infection of mice with Borrelia burgdorferi causes an inflammatory arthritis that peaks 3-4 wk postinfection and then spontaneously resolves. Although the recruitment of neutrophils is known to drive the development of arthritis, mechanisms of disease resolution remain unclear. Efficient clearance of apoptotic cells (AC) is likely an important component of arthritis resolution. In this article, we show the number of AC increases in the joints of B. burgdorferi-infected mice around day 21 postinfection and peaks around day 28. Injection of AC directly into the ankles of B. burgdorferi-infected mice limited ankle swelling but had no effect on spirochete clearance or arthritis severity scores. In vitro, addition of AC to bone marrow macrophage cultures decreased B. burgdorferi-induced TNF-α and KC and increased IL-10. In addition, phagocytosis of B. burgdorferi and neutrophil migration to LTB4 were inhibited by AC. Exogenous AC caused an increase in peroxisome proliferator-activated receptor-γ (PPAR-γ) expression both in vitro and in vivo during B. burgdorferi infection. The PPAR-γ agonist rosiglitazone elicited similar changes in macrophage cytokine production and neutrophil migration as exogenous AC. Addition of the PPAR-γ antagonist GW 9662 abrogated the effects of AC in vitro. Injection of rosiglitazone directly into the tibiotarsal joints of B. burgdorferi-infected mice decreased ankle swelling and immune cell recruitment, similar to the injection of AC.
These results suggest that clearance of AC plays a role in the resolution of inflammation during experimental Lyme arthritis through the activation of PPAR-γ. PPAR-γ agonists, such as rosiglitazone, may therefore be effective treatments for inducing arthritis resolution.
Apoptosis is programmed cell death without causing damage to other cells. https://science.howstuffworks.com/life/cellular-microscopic/apoptosis.htm
When cells recognize viruses and gene mutations, they may induce death to prevent the damage from spreading. In apoptosis the cell shrinks and sends out distress signals, which are answered by vacuum cleaners known as macrophages. The macrophages clean away the shrunken cells, leaving no trace.
Scientists are trying to learn how to modulate apoptosis, so that they can control which cells live and which undergo programmed cell death. Many diseases and disorders are linked with the life and death of cells such as AIDS & Parkinson’s. Decreased apoptosis can be a signal for lupus or cancer.
In the study above, they state that injecting the diabetic drug rosiglitazone (reduces blood glucose) into Bb infected mouse joints reduced swelling & immune cell recruitment similarly to injecting of apoptic cells.
Most interesting; however, is the admission that the injection of AC had no effect on spirochete clearance or arthritis severity scores.
So the question becomes once again, is getting rid of inflammation/swelling the sole issue for those of us “chronically/persistently” infected or is spirochete clearance important?
I predict that while rosigliazone might help with inflammation and pain (like so many other substances), spirochete clearance is still important.
This study begs the answer to what is causing persistent symptoms. I think it also important to suggest it may be a number of factors and it may vary from patient to patient.
If there’s one thing I’ve learned about Lyme/MSIDS, it’s that it is highly variable & complex.
What are the Similarities Between Autophagy and Apoptosis? https://www.differencebetween.com/difference-between-autophagy-and-vs-apoptosis/#Autophagy%20vs%20Apoptosis%20in%20Tabular%20Form
- Both result in programmed cell death.
- Both are natural phenomena.
- Both processes do not cause damage to other cells or cellular components.
- Both are important in development and normal physiology.
- Both are important in understanding the cellular basis of different pathological conditions including cancer and immune system related disorders.