Intestinal alkaline phosphatase

[Guest guest]

Dear All;

I've been reading about IBD and PSC for 4.5 years now, and I'm still suprised by what I don't know. This week I learned that intestinal alkaline phosphatase plays a major role in detoxifying lipopolysaccharide (LPS) [endotoxin]; the main component of the cell wall of Gram-negative bacteria that causes much of the inflammatory response associated with sepsis. The key reference is:

Cell Host Microbe. 2007 Dec 13;2(6):371-82. Intestinal alkaline phosphatase detoxifies lipopolysaccharide and prevents inflammation in zebrafish in response to the gut microbiota. Bates JM, Akerlund J, Mittge E, Guillemin K. Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA. PMID: 18078689.

http://download.cellhostandmicrobe.com/pdfs/1931-3128/PIIS1931312807002806.pdf

Apparently the intestinal alkaline phosphatase detoxifies LPS by dephosphorylating it, rendering it 100-times less toxic, and preventing intestinal inflammation. Although this was identified in an animal model (zebra fish) I wonder if this might be a gene of relevance to human IBD? Interesting the human intestinal alkaline phosphatase gene (IAP) is located very close to the ATG16L1 (autophagy) gene that has recently been identified as a Crohn's disease susceptibility gene at gene map locus 2q37.1:

http://www.ncbi.nlm.nih.gov/Omim/getmap.cgi?l171740

I also wonder whether biliary alkaline phosphatase might have a similar function in detoxifying LPS in the biliary tree? Is this relevant to PSC? Possibly. One group has shown that endotoxin (LPS) levels are significantly elevated in biliary epithelial cells of PSC patients:

J Hepatol. 1998 Sep;29(3):409-16. Abnormal accumulation of endotoxin in biliary epithelial cells in primary biliary cirrhosis and primary sclerosing cholangitis. Sasatomi K, Noguchi K, Sakisaka S, Sata M, Tanikawa K. PMID: 9764987.

Best regards,

Dave R.