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Chronic inflammation in the liver provokes fibrosis and, on long-term, carcinogenesis. This sequence is prototypically recapitulated in mice with hepatocyte-specific knock-out of the NF-κB essential modulator (NEMO), termed NEMO mice, in which increased hepatocyte apoptosis and compensatory regeneration cause steatosis, inflammation and fibrosis. Natural killer T (NKT) cells carrying the chemokine receptor CXCR6 participate in liver inflammation and injury responses. Here, we investigated the role of CXCR6 in the NEMO mouse model. Unexpectedly, genetic deletion of CXCR6 enhanced hepatocyte death, inflammation and fibrosis in NEMO mice. Although CXCR6 expression is restricted to immune cells in the liver, the adoptive transfer of CXCR6 cells did not protect NEMOCxcr6 mice from hepatic injury. Gene array analyses revealed up-regulated stress response and metabolism pathways in hepatocytes from NEMOCxcr6 mice, functionally corresponding to an increased susceptibility of these hepatocytes to TNFα-induced cell death in vitro. These data revealed a novel CXCR6-dependent mechanism of suppressing inflammatory hepatocytic responses to cellular stress.
This article was published in the following journal.
Name: Biochimica et biophysica acta. Molecular basis of disease
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A strain of mice widely studied as a model for cystic fibrosis. These mice are generated from embryonic stem cells in which the CFTR (cystic fibrosis transmembrane conductance regulator) gene is inactivated by gene targeting. As a result, all mice have one copy of this altered gene in all their tissues. Mice homozygous for the disrupted gene exhibit many features common to young cystic fibrosis patients, including failure to thrive, meconium ileus, and alteration of mucous and serous glands.
A group of interstitial lung diseases with no known etiology. There are several entities with varying patterns of inflammation and fibrosis. They are classified by their distinct clinical-radiological-pathological features and prognosis. They include IDIOPATHIC PULMONARY FIBROSIS; CRYPTOGENIC ORGANIZING PNEUMONIA; and others.
A common interstitial lung disease of unknown etiology, usually occurring between 50-70 years of age. Clinically, it is characterized by an insidious onset of breathlessness with exertion and a nonproductive cough, leading to progressive DYSPNEA. Pathological features show scant interstitial inflammation, patchy collagen fibrosis, prominent fibroblast proliferation foci, and microscopic honeycomb change.
A nonspecific tumor-like inflammatory lesion in the ORBIT of the eye. It is usually composed of mature LYMPHOCYTES; PLASMA CELLS; MACROPHAGES; LEUKOCYTES with varying degrees of FIBROSIS. Orbital pseudotumors are often associated with inflammation of the extraocular muscles (ORBITAL MYOSITIS) or inflammation of the lacrimal glands (DACRYOADENITIS).
Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.
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