Cellular intermediate filament networks and their derangement in alcoholic hepatitis

Intermediate filaments are major components of most eukaryotic cells that form from the polymerization of protein subunits that are expressed in tissue and development specific fashions. The interactions of intermediate filaments with a myriad of other cellular proteins and structures give rise to a complex overall cellular architecture that is likely responsible for cellular well-being. The mature 10-nm filaments are relatively stable cellular structures, but the intermediate filaments undergo major morphological and biochemical changes, especially during mitosis, differentiation, and in response to certain drugs. Evidence exists that hepatocyte intermediate filaments (keratin filaments) are deranged in alcoholic hepatitis, an inflammatory liver disease of alcoholics and heavy spree drinkers. The classical and characteristic pathological hepatocyte inclusion bodies of alcoholic hepatitis, Mallory bodies, are composed in part of normal keratins that likely derive from the pre-existing hepatocyte intermediate filament network. It is unclear if intermediate filament network derangement in alcoholic hepatitis is directly caused by the actions of ethanol or its metabolites on intermediate filaments or their associated structures, or whether alcohol causes a cellular insult or injury elsewhere and a subsequent response (e.g., immune) causes intermediate filament network derangement. The precise mechanisms responsible for intermediate filament derangement remain to be elucidated; however, experimental data exist that support and refute several hypotheses. Hopefully, further studies will help determine a better overall understanding of the abnormalities of intermediate filaments and their relationship to the pathophysiology of alcoholic hepatitis and other diseases.