Celery, green pepper compound may reduce inflammatory response in brain

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Washington, May 21 : University of Illinois researchers report a compound found in celery and green peppers can disrupt a key component of the inflammatory response in the brain.

Rodney Johnson of the University of Illinois at Urbana-Champaign and graduate student Saebyeol Jang found that a plant flavonoid, luteolin, inhibited a key pathway in the inflammatory response of microglia -- brain cells key to the body's immune defense.

The findings have implications for research on aging and diseases such as Alzheimer's and multiple sclerosis.

Inflammation is a critical part of the body's immune response that in normal circumstances reduces injury and promotes healing but can cause serious physical and mental problems when it goes awry.

Inflammation plays a key role in many neurodegenerative diseases and also is implicated in the cognitive and behavioural impairments seen in aging.

Researchers looked at luteolin, a plant flavonoid known to impede the inflammatory response in several types of cells outside the central nervous system.

Johnson said that the aim of the study was to find out if luteolin could also reduce inflammation in the brain and they started by first examining the effect of luteolin on microglia.

When infection occurs anywhere in the body, microglia respond by producing inflammatory cytokines, chemical messengers that act in the brain to orchestrate a whole-body response that helps fight the invading microorganism.

This response is linked to many of the most obvious symptoms of illness including sleepiness, loss of appetite, fever and lethargy, and sometimes a temporary diminishment of learning and memory.

Neuroinflammation can also lead some neurons to self-destruct, with potentially disastrous consequences if it goes too far.

Jang studied the inflammatory response in microglial cells and found that those cells that were also exposed to luteolin showed a significantly diminished inflammatory response.

She showed that luteolin was shutting down production of a key cytokine in the inflammatory pathway, interleukin-6 (IL-6).

The effects of luteolin exposure were dramatic, resulting in as much as a 90 percent drop in IL-6 production in the LPS-treated cells.

"This was just about as potent an inhibition as anything we had seen previously," Johnson said.

However, researchers also wanted to find out how was luteolin inhibiting production of IL-6.

They began by looking at a class of proteins involved in intracellular signalling, called transcription factors, which bind to specific 'promoter' regions on DNA and increase their transcription into RNA and translation into proteins.

Using electromobility shift assays, which measure the binding of transcription factors to DNA promoters, Jang eventually determined that luteolin inhibited IL-6 production by preventing activator protein-1 (AP-1) from binding the IL-6 promoter.

AP-1 is in turn activated by JNK, an upstream protein kinase. Jang found that luteolin inhibited JNK phosphorylation in microglial cell culture.

The failure of the JNK to activate the AP-1 transcription factor prevented it from binding to the promoter region on the IL-6 gene and transcription came to a halt.

In order to determine if luteolin might have a similar effect in vivo, the researchers gave mice luteolin-laced drinking water for 21 days before injecting the mice with LPS.

Those mice that were fed luteolin had significantly lower levels of IL-6 in their blood plasma four hours after injection with the LPS.

Luteolin also decreased LPS-induced transcription of IL-6 in the hippocampus, a brain region that is critical to spatial learning and memory.

Johnson said that the findings indicate a possible role for luteolin or other bioactive compounds in treating neuroinflammation.

The study appears this week in Proceedings of the National Academy of Sciences.

ANI

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