Carbon monoxide protects against paralysis in MS mice
{{date|January 26, 2007}}

[[Image:Monthly multiple sclerosis MRI.gif|right|thumb|300px|T1-weighted [[w:magnetic resonance imaging|MRI]] brain slices from a patient with multiple sclerosis at monthly intervals. Bright spots indicate active lesions.]]

Ângelo A. Chora ''et. al.'' are reporting in the [[w:Journal of Clinical Investigation|Journal of Clinical Investigation]] this week that [[w:carbon monoxide|carbon monoxide]] (CO) and the [[w:Heme oxygenase|heme oxygenase-1 protein]] protect against the symptoms of [[w:multiple sclerosis|multiple sclerosis]] (MS) in the related mouse model of [[w:Experimental autoimmune encephalomyelitis|experimental autoimmune encephalomyelitis]] (EAE).

Multiple sclerosis is a chronic, inflammatory disease that affects the [[w:Central nervous system|central nervous system]] (CNS). Although many patients are largely unaffected by their disease, MS can cause impaired mobility and disability in more severe cases.

The research group from the Gulbenkian Institute in [[Portugal]] used the EAE mouse model of MS to study the effects of the Heme oxygenase-1 (HO-1) protein encoded by the HMOX1 gene.

HO-1 [[w:Knockout mouse|knockout mice]], lacking both copies of the gene (not producing the [[w:protein|protein]]), showed a more severe progression of the disease compared to wild-type mice, having normal levels of the protein. The symptoms of the disease were reversed when the HO-1 protein expression was induced using cobalt [[w:Porphyrin|protoporphyrin]] IX.

During MS attacks the body's own [[w:Immune system|immune system]] destroys the [[w:Myelin|myelin sheath]] surrounding [[w:Neuron|nerve cells]] in the brain and spinal cord. Pathogenic [[w:T helper cell|T helper cells]] are triggered by [[w:antigen-presenting cell|Antigen-presenting cell]] (APCs) within the brain stem. The disease can cycle between attacks (relapses) followed by remission, suggesting that there is an underlying regulatory system. The HO-1 protein had been identified previously as a possible candidate for a protective gene.

HO-1 degrades excess [[w:heme|heme]] within the body acting as the rate controlling step when under inflammatory conditions. The HO-1 heme degradation pathway produces as products equal amounts of free heme, carbon monoxide and [[w:biliverdin|biliverdin]].

Carbon monoxide was also shown to limit the effects of the disease. Mice were exposed to a high concentration of CO for 20 days within a chamber. Mice exposed to CO had limp tails, but were more mobile than the mice in the control experiment which displayed hind limb [[w:paralysis|paralysis]].

It is still unknown exactly how carbon monoxide slows down the symptoms of EAE, possibly through the mopping up of [[w:Free radicals|free radicals]], or through promoting the binding of iron to heme (decreasing radical production).

The experiments found that HO-1 did not affect the development or function of [[w:regulatory T cells|regulatory T cells]]. For a beneficial effect HO-1 needed to be expressed in [[w:dendritic cells|dendritic cells]], causing inhibition of [[w:Major histocompatibility complex|MHC-II proteins]], involved in presenting antigens, and inflammatory cytokines ([[w:Interferon-gamma|IFN-γ]]).

These experiments open up new possibilities for MS therapies, involving the expression of HO-1 in suppressing the development of MS.

The article went online on the 25th January 2007 and will be printed in the Journal of Clinical Investigation in February.

== Sources ==
*{{source|url=http://www.jci.org/
|title=Heme oxygenase–1 and carbon monoxide suppress autoimmune neuroinflammation
|author=Ângelo A. Chora et al
|pub=Journal of Clinical Investigation 
|date=January 25, 2007}}
*{{source|url=http://www.newscientist.com/article.ns?id=dn11036
|title=Carbon monoxide may protect against MS symptoms
|author=Roxanne Khamsi
|pub=New Scientist
|date=January 26, 2007}}
*{{source|url=http://www.sciencedaily.com/releases/2007/01/070125190053.htm
|title=Carbon Monoxide Protects Mice From Multiple Sclerosis
|author=
|pub=Science Daily
|date=January 26, 2007}}

{{publish}}
{{archive}}
[[Category:Science and technology]]
[[Category:Biotechnology]]
[[Category:Health]]
[[Category:Portugal]]
[[Category:Biology]]
MRI brain slices from a patient with multiple sclerosis at monthly intervals. Bright spots indicate active lesions.

Ângelo A. Chora et. al. are reporting in the Journal of Clinical Investigation this week that carbon monoxide (CO) and the heme oxygenase-1 protein protect against the symptoms of multiple sclerosis (MS) in the related mouse model of experimental autoimmune encephalomyelitis (EAE).

Multiple sclerosis is a chronic, inflammatory disease that affects the central nervous system (CNS). Although many patients are largely unaffected by their disease, MS can cause impaired mobility and disability in more severe cases.

The research group from the Gulbenkian Institute in Portugal used the EAE mouse model of MS to study the effects of the Heme oxygenase-1 (HO-1) protein encoded by the HMOX1 gene.

HO-1 knockout mice, lacking both copies of the gene (not producing the protein), showed a more severe progression of the disease compared to wild-type mice, having normal levels of the protein. The symptoms of the disease were reversed when the HO-1 protein expression was induced using cobalt protoporphyrin IX.

During MS attacks the body's own immune system destroys the myelin sheath surrounding nerve cells in the brain and spinal cord. Pathogenic T helper cells are triggered by Antigen-presenting cell (APCs) within the brain stem. The disease can cycle between attacks (relapses) followed by remission, suggesting that there is an underlying regulatory system. The HO-1 protein had been identified previously as a possible candidate for a protective gene.

HO-1 degrades excess heme within the body acting as the rate controlling step when under inflammatory conditions. The HO-1 heme degradation pathway produces as products equal amounts of free heme, carbon monoxide and biliverdin.

Carbon monoxide was also shown to limit the effects of the disease. Mice were exposed to a high concentration of CO for 20 days within a chamber. Mice exposed to CO had limp tails, but were more mobile than the mice in the control experiment which displayed hind limb paralysis.

It is still unknown exactly how carbon monoxide slows down the symptoms of EAE, possibly through the mopping up of free radicals, or through promoting the binding of iron to heme (decreasing radical production).

The experiments found that HO-1 did not affect the development or function of regulatory T cells. For a beneficial effect HO-1 needed to be expressed in dendritic cells, causing inhibition of MHC-II proteins, involved in presenting antigens, and inflammatory cytokines (IFN-γ).

These experiments open up new possibilities for MS therapies, involving the expression of HO-1 in suppressing the development of MS.

The article went online on the 25th January 2007 and will be printed in the Journal of Clinical Investigation in February.
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