Pantethine may exacerbate inflammation in colitis
Kofi
Sympathetic tone has long been known to exacerbate acute colitis while
ameliorating the chronic condition. It may be the case that Vanin-1
(pantetheinase) has the same dual effects and they only caught the acute
effects.
Inflamm Bowel Dis. 2009 Jul 1
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Epithelial vanin-1 controls inflammation-driven carcinogenesis in the
colitis-associated colon cancer model.
Pouyet L, Roisin-Bouffay C, Clement A, Millet V, Garcia S, Chasson L,
Issaly N, Rostan A, Hofman P, Naquet P, Galland F.
Aix Marseille Universite, Faculte des Sciences de Luminy, Centre
d'Immunologie de Marseille-Luminy, Marseille, France.
BACKGROUND:: Vanin-1 is an epithelial pantetheinase that provides
cysteamine to tissue and regulates response to stress. Vanin-1 is
expressed by enterocytes, and its absence limits intestinal epithelial
cell production of proinflammatory signals. A link between chronic
active inflammation and cancer is illustrated in patients with
ulcerative colitis, who have an augmented risk of developing colorectal
cancer. Indeed, sustained inflammation provides advantageous growth
conditions to tumors. We examined whether epithelial cells affect
tumorigenesis through vanin-1-dependent modulation of colonic
inflammation. METHODS:: To vanin-1(-/-) mice, we applied the
colitis-associated cancer (CAC) protocol, which combines injection of
azoxymethane (AOM) with repeated administrations of dextran sodium
sulfate (DSS). We numbered tumors and quantified macrophage infiltration
and molecular markers of cell death and proliferation. We also tested
DSS-induced colitis. We scored survival, tissue damages, proinflammatory
cytokine production, and tissue regeneration. Finally, we explored
activation pathways by biochemical analysis on purified colonic
epithelial cells (CECs) and in situ immunofluorescence. RESULTS::
Vanin-1(-/-) mice displayed a drastically reduced incidence of
colorectal cancer in the CAC protocol and manifested mild clinical signs
of DSS-induced colitis. The early impact of vanin-1 deficiency on tumor
induction was directly correlated to the amount of inflammation and
subsequent epithelial proliferation rather than cell death rate; all
this was linked to the modulation of NF-kappaB pathway activation in
CECs. CONCLUSIONS:: These results emphasize the importance of the
intestinal epithelium in the control of mucosal inflammation acting as a
cofactor in carcinogenesis. This might lead to novel anti-inflammatory
strategies useful in cancer therapy. Inflamm Bowel Dis 2009.
PMID: 19572375