%0 Journal Article %T Keratins provide virus-dependent protection or predisposition to injury in coxsackievirus-induced pancreatitis %A DM Toivola %A SE Ostrowski %A H Baribault %A et al %J Cell Health and Cytoskeleton %D 2009 %I %R http://dx.doi.org/10.2147/CHC.S5792 %X atins provide virus-dependent protection or predisposition to injury in coxsackievirus-induced pancreatitis Original Research (4039) Total Article Views Authors: DM Toivola, SE Ostrowski, H Baribault, et al Published Date August 2009 Volume 2009:1 Pages 51 - 65 DOI: http://dx.doi.org/10.2147/CHC.S5792 DM Toivola1, SE Ostrowski2, H Baribault3, TM Magin4, AI Ramsingh2, MB Omary5 1 bo Akademi University, Dept. Biology, BioCity, Turku, Finland and Stanford University School of Medicine and Digestive Disease Center; 2New York State Department of Health, Albany, NY, USA; 3Amgen, South San Francisco, CA, USA; 4University of Bonn, Bonn, Germany; 5Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, Mi, USA Abstract: Keratins 8 and 18 (K8/K18) are the two major intermediate filament proteins in hepatocytes and pancreatic acinar cells. Acinar cell keratins are organized as cytoplasmic and apicolateral filaments. An important role of hepatocyte K8/K18 is to maintain cellular integrity, while this cytoprotective function of K8/K18 is not evident in the pancreas since keratin-deficient mice cope well with pancreatitis models. To further study the roles of keratins in the exocrine pancreas, we used coxsackievirus B4-models, CVB4-V and CVB4-P, to induce severe acute/chronic pancreatitis and acute pancreatitis, respectively, in K8-null (which lack acinar keratins) and K18-null (which lack cytoplasmic keratins) mice. Despite similar virus titers in all mice, CVB4-V resulted in 40% mortality of the K8-null mice 14 days post-infection compared to no lethality of WT and K18-null mice. In contrast, K8-null mice were far less susceptible to CVB4-P-induced damage as determined by histology and serology analysis, and they recover faster than WT and K18-null mice. After CVB4 virus infection, keratins aggregated during acinar degranulation, and K8/K18 site-specific phosphorylation was observed during degranulation and recovery. Hence, keratins significantly affect CVB4 virulence, positively or negatively, depending on the virus subtype and keratin makeup, in a virus replication-independent manner. %K keratin %K pancreatitis %K coxsackievirus %U https://www.dovepress.com/keratins-provide-virus-dependent-protection-or-predisposition-to-injur-peer-reviewed-article-CHC