chapter  Chapter 7
8 Pages

Effects of Cytokines and Nitric Oxide on Bicarbonate Secretion by Cholangiocytes

WithCarlo Spirlì, Lajos Okolicsanyi, Mario Strazzabosco

The hallmark of cholangiopathies (i.e., diseases of the intrahepatic biliary ducts) is a chronic progressive cholestasis. Cytokines and other inflammatory mediators play a central role in the pathophysiology of cholangiopathies through stimulation of apoptotic and proliferative responses, activation of reparative/fibrogenetic processes and induction of cell damage. The effects of inflammatory mediators on cholangiocytes secretory mechanisms are currendy under investigation.

In this chapter we describe how inflammatory mediators (IL-1, IL-6, TNFα, IFNγ, and nitric oxide) contribute to cholestasis by alteration of cAMP-dependent electrolyte transport into the bile, a major function of the biliary epithelium. Available evidences suggest that these mediators inhibit cAMP formation by adenylyl cyclase, resulting in an inhibition of cAMP-dependent Cl transport by CFTR and HCO3 transport by Cl/HCO3 exchanger.

Ductal cholestasis, i.e. reduced fluid and electrolyte transport by cholangiocytes, is a central step in the pathogenetic sequence of cholangiopathies and predisposes the biliary epithelium to further damage. Better understanding the role of inflammation may help to design new strategies to modulate cholangiocyte secretory mechanisms in cholestasis.