Crohn's, NOD2 and cathelicidin (and P2X7)
Kofi
played a role in gut barrier integrity and, if it did, it was probably
wrapped up in the cathelicidin signaling system. Bingo. For the link,
see PMID 19544485.
So there's a deep connection between NOD2 and cathelicidin. Break NOD2
and you are definitely breaking part of cathelicidin's function in the
gut. Cathelicidin is crucial to gut barrier integrity and relies on the
P2X7 ATP receptor (which is why trying to treat spinal injuries with
Brilliant Blue G to block P2X7 could cause sepsis, by the way). It's
possible the NOD2 problem explains the deficiency in cathelicidin seem
in Crohn's.
In article
<9728352b-cebf-4867...@b15g2000yqd.googlegroups.com>,
zumone2002 <zumon...@yahoo.com> wrote:
> http://www.eurekalert.org/pub releases/2009-07/muhc-tae070909.php
>
> Toward an explanation for Crohn's disease?
> An innovative study at the Research Institute of the MUHC has brought
> us closer to an explanation for Crohn's disease
>
> This release is available in French.
>
> Montreal, July 9th 2009 � Twenty-five per cent of Crohn's disease
> patients have a mutation in what is called the NOD2 gene, but it is
> not precisely known how this mutation influences the disease. The
> latest study by Dr. Marcel Behr, of the Research Institute of the MUHC
> and McGill University, has provided new insight into how this might
> occur. The study will be published on July 9th in the Journal of
> Experimental Medicine.
>
> When the NOD2 gene functions normally, it codes for a receptor that
> will recognize invading bacteria and then trigger the immune response.
> This study demonstrates that the NOD2 receptor preferentially
> recognizes a peptide called N-glycolyl-MDP, which is only found in a
> specific family of bacteria called mycobacteria. When mycobacteria
> invade the human body, they cause an immediate and very strong immune
> response via the NOD2 receptor.
>
> "Now that we have a better understanding of the normal role of NOD2,
> we think that a mutation in this gene prevents mycobacteria from being
> properly recognized by the immune system," explained Dr. Behr. "If
> mycobacteria are not recognized, the body cannot effectively fight
> them off and then becomes persistently infected."
>
> Researchers were already aware of the relationship between
> mycobacteria and Crohn's disease, but they did not know whether the
> presence of bacteria was a cause or a consequence of the disease. This
> new discovery associates the predisposition for Crohn's disease with
> both the NOD2 mutation and the presence of mycobacteria, but
> researchers must still determine the precise combination of these
> factors to understand how the disease develops.
>
> More research is required to establish a complete explanation. From
> this, it is expected that new therapeutic approaches that fight the
> cause of Crohn's disease may be developed
>
> --
> Luke
trigonometry1972@gmail.com |
Transcriptional and inflammasome-mediated pathways
for the induction of IL-1beta production by Mycobacterium
tuberculosis.
Kleinnijenhuis J, Joosten LA, van de Veerdonk FL,
Savage N, van Crevel R, Kullberg BJ, van der Ven A,
Ottenhoff TH, Dinarello CA, van der Meer JW, Netea
MG.
Department of Medicine,
Radboud University Nijmegen Medical Center,
The Netherlands.
m.n...@aig.umcn.nl
Proinflammatory cytokines of the IL-1 family play an important
role for the anti-mycobacterial host defense mechanisms.
In the present study we have deciphered the pathways leading
from recognition of Mycobacterium tuberculosis to
the production and release of IL-1beta, the most
important member of the IL-1 family. By stimulating cells
defective in various pattern recognition receptors,
we could demonstrate that IL-1beta production is induced
by M. tuberculosis through pathways involving TLR2/TLR6
and NOD2 receptors. In contrast, TLR4, TLR9
and TLR1 receptors are not involved in IL-1beta induction.
Recognition of M. tuberculosis by TLR and NOD2 leads to
transcription of proIL-1beta through mechanisms involving
ERK, p38 and Rip2, but not JNK. Interestingly, although
caspase-1 is necessary for the processing of proIL-1beta,
activation of caspase-1 is not dependent on the stimulation
of cells by M. tuberculosis. Monocytes expressed constitutively
active caspase-1. The secretion of IL-1beta is dependent
on the activation of P2X7-induced pathways by
endogenously released ATP. In conclusion, we have
dissected the molecular mechanisms responsible for
IL-1beta production by M. tuberculosis, and that may
contribute to a deeper knowledge of the mechanisms of
cell activation by M. tuberculosis.
PMID: 19544485