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It is a VERY GOOD IDEA to lower MMP-9s if taking an Ifn-Beta drug.
If you want to maximize Avonex (or any beta interferon), lowering MMP-9s will prevent it from being degraded by being cleaved into parts thus killing its Activity/Effectiveness.
Also getting the most activity from the least amount of near natural (human) interferon like Avonex will usually result in MUCH LESS neutralizing antibody formation (2-5% vrs 20-26%).
Things that reduce MMP-9s (AKA gelatinase B)
VIT D3 .................................REDUCES MMP-9s
Chondroitin sulfate (CS) and CS plus glucosamine sulfate (GS) ..REDUCES MMP-9s
Interferon Betas 1a/1b...........REDUCES MMP-9
(of course Steroids ....REDUCES MMP-9s)
***NOTE*** ( gelatinase B = MMP-9) ***NOTE***
I have lots more information on this MMP - MS - INTERFERON-beta connection and will elaborate it if there is some interest in this subject here. For the real techie stuff check the link shown below
Functional roles and therapeutic targeting of gelatinase B and chemokines in
multiple sclerosis.
Opdenakker G, Nelissen I, Van Damme J.
GO, IN, and JVD are at the Rega Institute for Medical Research, University
of
Leuven, Belgium
Multiple sclerosis (MS) is a demyelinating disease of the CNS of unknown
cause. Pathogenetic mechanisms, such as chemotaxis, subsequent activation of
autoreactive lymphocytes, and skewing of the extracellular proteinase
balance, are targets for new therapies.
Matrix metalloproteinase gelatinase B (MMP-9) is upregulated in MS and was
recently shown to degrade interferon beta, one of the drugs used to treat
MS.
Consequently, the effect of endogenously produced interferon beta or
parenterally given interferon beta may be increased by gelatinase B
inhibitors. Blockage of chemotaxis or cell adhesion molecule engagement, and
inhibition of hydoxymethyl-glutaryl-coenzyme-A reductase to lower expression
of gelatinase B, may become effective treatments of MS, alone or in
combination with interferon beta. This may allow interferon beta to be used
at lower doses and prevent side-effects.
PMID: 14636780 [PubMed - in process]
1: Brain. 2003 Jun;126(Pt 6):1371-81.
Gelatinase B/matrix metalloproteinase-9 cleaves interferon-beta and is a
target for immunotherapy.
Nelissen I, Martens E, Van den Steen PE, Proost P, Ronsse I, Opdenakker G.
Rega Institute for Medical Research, Laboratory of Molecular Immunology,
University of Leuven, Leuven, Belgium.
Parenteral administration of interferon (IFN)-beta is one of the currently
approved therapies for multiple sclerosis. One characteristic of this
disease is the increased production of gelatinase B, also called matrix
metalloproteinase (MMP) 9. Gelatinase B is capable of destroying the
blood-brain barrier, and of cleaving myelin basic protein into
immunodominant and encephalitogenic fragments, thus playing a functional
role and being a therapeutic target in multiple sclerosis. Here we
demonstrate that gelatinase B proteolytically cleaves IFN-beta, kills its
activity, and hence counteracts this cytokine as an antiviral and
immunotherapeutic agent. This proteolysis is more pronounced with
IFN-beta-1b than with IFN-beta-1a. Furthermore, the tetracycline
minocycline, which has a known blocking effect in experimental autoimmune
encephalomyelitis, an in vivo model of acute inflammation in multiple
sclerosis, and other MMP inhibitors prevent the in vitro degradation of
IFN-beta by gelatinase B. These data provide a novel mechanism and rationale
for the inhibition of gelatinase B in diseases in which IFN-beta has a
beneficial effect. The combination of gelatinase B inhibitors with better
and lower pharmacological formulations of IFN-beta may reduce the
side-effects of treatment with IFN-beta, and is therefore proposed for
multiple sclerosis therapy and the immunotherapy of viral infections.
PMID: 12764058 [PubMed - indexed for MEDLINE]
1: Neuroscientist 2002 Dec;8(6):586-95
Matrix metalloproteinases and neuroinflammation in multiple sclerosis.
Rosenberg GA.
Department of Neurology, University of New Mexico Health Sciences Center,
Albuquerque, New Mexico 87131, USA.
Matrix metalloproteinases (MMPs) are extracellular matrix remodeling neutral proteases that are important in normal development, angiogenesis, wound repair, and a wide range of pathological processes. Growing evidence supports a key role of the MMPs in many neuroinflammatory conditions, including meningitis, encephalitis, brain tumors, cerebral ischemia, Guillain-Barre, and multiple sclerosis (MS).
The MMPs attack the basal lamina macromolecules that line the blood vessels, opening the blood-brain barrier (BBB). They contribute to the remodeling of the blood vessels that causes hyalinosis and gliosis, and they attack myelin. During the acute inflammatory phase of MS, they are involved in the injury to the blood vessels and may be important in the disruption of the myelin sheath and axons. Normally under tight regulation, excessive proteolytic activity is detected in the blood and cerebrospinal fluid in patients with acute MS. Because they are induced in immunologic and nonimmunologic forms of demyelination, they act as a final common pathway to exert a "bystander" effect.
AGENTS THAT BLOCK THE ACTION OF THE MMPS HAVE BEEN SHOWN TO REDUCE THE DAMAGE TO THE BBB AND LEAD TO SYMPTOMATIC IMPROVEMENT IN SEVERAL ANIMAL MODELS OF NEUROINFLAMMATORY DISEASES, INCLUDING EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS. SUCH AGENTS MAY EVENTUALLY BE USEFUL IN THE CONTROL OF EXCESSIVE PROTEOLYSIS THAT CONTRIBUTES TO THE PATHOLOGY OF MS AND OTHER NEUROINFLAMMATORY CONDITIONS.
jackD? THE jackD?! Of Braintalk fame? I think I'd recognize your unique posting style anywhere. Welcome to ThisIsMS. I don't know for sure, but I think you might like it here...
Joined: May 25, 2006 Posts: 27 Location: Near Wash DC
Posted: Mon Jul 02, 2007 10:50 pm Post subject:
Thanks for the welcome.
I posted all this stuff before in 2000-2001-2002 before in alt.support.mult-sclerosis before all the great validating studies were published. I seem to be alone in the lowering MMP-9 approach. It is a bit strange that the rest of the MS world in some other discussion groups are in such a "Pity Party" mood and cannot see how simple it is to help the Avonex and other IFN-Betas work better.
Taking lots of VIT D3(4,000-5,000 ius) and lowering MMP-9s and capping TNF-a, IL-12, IL-1beta and Gamma Interferon will really maximize the effectiveness of the IFN-Beta and allow it to do its work.
The disappointing fact about Avonex and other IFN-Betas is that they are ineffective during relapses because of the high MMP-9 levels and they take about 6 months before the full effects show up. Long term Avonex seems to be the best. I took it for 10 years and I am doing OK.
Joined: Feb 07, 2007 Posts: 16 Location: near Chicago, IL
Posted: Sun Jul 08, 2007 7:24 pm Post subject:
Apologies if this is a stupid question.
I thought that ECGC (in green tea) actually enhanced immune function, and so was not a good idea for those trying to suppress their immune system. I stopped drinking green tea when I started Avonex. Is green tea actually a good idea when on Avonex, based on what you are saying?
Joined: May 25, 2006 Posts: 27 Location: Near Wash DC
Posted: Sun Jul 08, 2007 11:44 pm Post subject: Green Tea & MMP-9s Multiple Sclerosis
Green Tea & MMP-9s
Green Tea is a winner!!
HOWEVER Drinking a cup or two WILL NOT HELP MUCH!!!~
Get some MEGA GREEN TEA EXTRACT from LEF.ORG and take two a day.
I still have a large pot of Green & White tea tea each day.
Lainie You should re-read my first post again and check the links.
MMP-9s KILL Interferon Betas (AVONEX). Cleaves it into little pieces, makes it inert. I thought I made that point.
MMP-9s cut hole in BBB (Blood Brain Barrier) and then proceed to cut myelin into three components that other immune players love to dine on.
That is why reducing them is such a good idea.
Green Tea is protective in many ways without actually enhancing the immune function. It fights Cancer,inflammation and lowers MMP-9s levels. MMP-9s also make some nasty versions of TNF-a.
Some VERY VERY simple supplements can do the job quite well with almost no side effects. I do not take MEGA doses of any of them except green tea. I also take four different kinds/brands of Reseratrol plus a glass and a half of some Great red wine each day.
jackD
J Immunol. 2004 Nov 1;173(9):5794-800.
Green tea epigallocatechin-3-gallate mediates T cellular NF-kappa B inhibition and exerts neuroprotection in autoimmune encephalomyelitis.
Aktas O, Prozorovski T, Smorodchenko A, Savaskan NE, Lauster R, Kloetzel PM, Infante-Duarte C, Brocke S, Zipp F.
Institute of Neuroimmunology, Neuroscience Research Center, Charité, Berlin, Germany.
Recent studies in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), point to the fact that even in the early phase of inflammation, neuronal pathology plays a pivotal role in the sustained disability of affected individuals.
We show that the major green tea constituent, (-)-epigallocatechin-3-gallate (EGCG), dramatically suppresses EAE induced by proteolipid protein 139-151.
EGCG reduced clinical severity when given at initiation or after the onset of EAE by both limiting brain inflammation and reducing neuronal damage. In orally treated mice, we found abrogated proliferation and TNF-alpha production of encephalitogenic T cells. In human myelin-specific CD4+ T cells, cell cycle arrest was induced, down-regulating the cyclin-dependent kinase 4. Interference with both T cell growth and effector function was mediated by blockade of the catalytic activities of the 20S/26S proteasome complex, resulting in intracellular accumulation of IkappaB-alpha and subsequent inhibition of NF-kappaB activation. Because its structure implicates additional antioxidative properties, EGCG was capable of protecting against neuronal injury in living brain tissue induced by N-methyl-D-aspartate or TRAIL and of directly blocking the formation of neurotoxic reactive oxygen species in neurons. Thus, a natural green tea constituent may open up a new therapeutic avenue for young disabled adults with inflammatory brain disease by combining, on one hand, anti-inflammatory and, on the other hand, neuroprotective capacities.
We have investigated the effects of different biologically active components from natural products, including green tea polyphenols (GTP), resveratrol, genistein and organosulfur compounds from garlic, on matrix metalloproteinase (MMP)-2, MMP-9 and MMP-12 activities. GTP caused the strongest inhibition of the three enzymes, as measured by fluorescence assays using gelatin or elastin as substrates. The inhibition of MMP-2 and MMP-9 caused by GTP was confirmed by
gelatin zymography and was observed for MMPs associated with both various rat tissues and human brain tumors (glioblastoma and pituitary tumors). The activities of MMPs were also measured in the presence of various catechins isolated from green tea including (-)-epigallocatechin gallate (EGCG), (-)-epicatechin gallate(ECG), (-)-epigallocatechin (EGC), (-)-epicatechin (EC) and (+)-catechin (C). The most potent inhibitors of these activities, as measured by fluorescence and by gelatin or casein zymography, were EGCG and ECG. GTP and the different catechins had no effect on pancreatic elastase, suggesting that the effects of these molecules on MMP activities are specific.
Furthermore, in vitro activation of proMMP-2 secreted from the glioblastomas cell line U-87 by the lectin concanavalin A was completely inhibited by GTP and specifically by EGCG. These results indicate that catechins from green tea inhibit MMP activities and proMMP-2 activation.
PMID: 10719174 [PubMed - indexed for MEDLINE]
Last edited by jackD on Mon Jul 09, 2007 1:59 am; edited 2 times in total
Theanine is an amino acid found in green tea that produces
tranquilizing effects in the brain. In Japan, soft drinks and
chewing gum are spiked with theanine for the purpose of
inducing relaxation.
Although theanine creates a feeling of
relaxation, it doesn't shut down the brain. Studies on rodents
show that theanine enhances the ability to learn and remember.
By shutting off worry central, theanine appears to increase
concentration and focus thought.
Theanine is different than kava-kava in that it doesn't cause
drowsiness, just relaxation. Theanine increases GABA, while
caffeine decreases it. GABA doesn't just relax, it also
creates a sense of well-being. Theanine's ability to increase
this brain chemical can literally put you in a better mood.
Theanine also increases levels of dopamine, another brain
chemical with mood-enhancing effects.
Protecting neurons
In studies on neurons in cell culture, theanine significantly
reverses glutamate-induced toxicity. In vivo studies show the
same effect in rodents. Glutamate-induced neuro-toxicity is a
major cause of degenerative brain disease.
Many Americans suffer from slightly elevated blood pressure,
but don't know they have it. Chronic high blood pressure
inflicts damage on the delicate cerebral vascular network and
increases the risk of stroke. Theanine has been shown to help
lower blood pressure.
Theanine readily crosses the blood-brain barrier and changes
brain chemistry in a way that has been compared to
aromatherapy. Studies show that theanine is a non-toxic,
highly desirable mood modulator that can be enjoyed by
everyone except babies.
1: Biol Pharm Bull. 2002 Dec;25(12):1513-8.
Neuroprotective effects of the green tea components theanine and catechins.
Kakuda T.
Central Research Institute, Itoen, Ltd, Shuzuoka, Japan.
The neuroprotective effects of theanine and catechins contained in green tea are discussed. Although the death of cultured rat cortical neurons was induced by the application of glutamic acid, this neuronal death was suppressed with exposure to theanine. The death of hippocampal CA1 pyramidal neurons caused by transient forebrain ischemia in the gerbil was inhibited with the ventricular preadministration of theanine. The neuronal death of the hippocampal CA3 region by kainate was also prevented by the administration of theanine. Theanine has a higher binding capacity for the AMPA/kainate receptors than for NMDA receptors,
although the binding capacity in all cases is markedly less than that of
glutamic acid.
The results of the present study suggest that the mechanism of the neuroprotective effect of theanine is related not only to the glutamate
receptor but also to other mechanisms such as the glutamate transporter,
although further studies are needed. One of the onset mechanisms for
arteriosclerosis, a major factor in ischemic cerebrovascular disease, is
probably the oxidative alteration of low-density lipoprotein (LDL) by active
oxygen species. The oxidative alterations of LDL were shown to be prevented by tea catechins. Scavenging of *O(2)(-) was also exhibited by tea catechins.
The neuroprotective effects of theanine and catechins contained in green tea are a focus of considerable attention, and further studies are warranted.
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If you want to maximize Avonex (or any beta interferon), lowering MMP-9s will prevent it from being degraded by being cleaved into parts thus killing its Activity/Effectiveness.
We show that the major green tea constituent, (-)-epigallocatechin-3-gallate (EGCG), dramatically suppresses EAE induced by proteolipid protein 139-151.
The most potent inhibitors of these activities, as measured by fluorescence and by gelatin or casein zymography, were EGCG and ECG. GTP and the different catechins had no effect on pancreatic elastase, suggesting that the effects of these molecules on MMP activities are specific.