Re: World Journal of Gastroenterology (Jan 2008)/Smoking issue

[Guest guest]

Hi Penny;

There was a poll conducted earlier on this, but the poll is now closed. Results are that the vast majority of respondents are non-smokers:

http://health.groups.yahoo.com/group//surveys?id=1409736

In my opinion, one of the best explantions about this relationship between PSC, UC and non-smoking status seems to be that nicotine has a significant effect on gut epithelial permeability .... it affects the level of expression of proteins called tight junction proteins that function to keep the cells held tightly together:

McGilligan VE, Wallace JM, Heavey PM, Ridley DL, Rowland IR 2007 The effect of nicotine in vitro on the integrity of tight junctions in Caco-2 cell monolayers. Food Chem. Toxicol. 45: 1593-1598.

There is genetic evidence that a defect in one of these tight junction proteins (claudin-1) results in neonatal sclerosing cholangitis:

Hadj-Rabia S, Baala L, Vabres P, Hamel-Teillac D, Jacquemin E, Fabre M, Lyonnet S, De Prost Y, Munnich A, Hadchouel M, Smahi A 2004 Claudin-1 gene mutations in neonatal sclerosing cholangitis associated with ichthyosis: a tight junction disease. Gastroenterology 127: 1386-1390.

For these reasons I'm interested in nutritional factors that may increase epithelial integrity. One factor seems to be retinoic acid (derived from Vitamin A):

Osanai M, Nishikiori N, Murata M, Chiba H, Kojima T, Sawada N 2007 Cellular retinoic acid bioavailability determines epithelial integrity: role of retinoic acid receptor alpha agonists in colitis. Mol. Pharmacol. 71: 250-258.

And another seems to be n-3 polyunsaturated fatty acids (fish oils):

Li Q, Zhang Q, Zhang M, Wang C, Zhu Z, Li N, Li J 2008 Effect of n-3 polyunsaturated fatty acids on membrane microdomain localization of tight junction proteins in experimental colitis. FEBS J. 275: 411-420.

This would not be inconsistent with some of the prevailing hypotheses about the pathogenesis of PSC. For example, Cullen and Chapman (2001) state:

"PSC may be triggered in genetically susceptible individuals by toxic or infectious agents gaining access to the liver via a diseased and permeable colon."

Cullen S, Chapman R 2001 Aetiopathogenesis of primary sclerosing cholangitis. Best Pract. Res. Clin. Gastroenterol. 15: 577-589.

Best regards,

Dave

(father of (22); PSC 07/03; UC 08/03)

> >> > A recent volume (14(3)) of World Journal of Gastroenterology (Jan > > 2008) is worth a close look. Some good articles in this issue are:> > > > Primary sclerosing cholangitis, autoimmune hepatitis and overlap > > syndromes in inflammatory bowel disease> > Saich, Chapman> > http://www.wjgnet.com/1007-9327/14/331.asp> >>