Defects in Actin Dynamics Lead to an Autoinflammatory Condition through the Upregulation of CXCL5

Destrin (DSTN) is a member of the ADF/cofilin family of proteins and is an important regulator of actin dynamics. The primary function of destrin is to depolymerize filamentous actin into its monomeric form and promote filament severing. While progress has been made in understanding the biochemical functions of the ADF/cofilin proteins, the study of an animal model for cells deficient for DSTN provides an opportunity to investigate the physiological processes regulated by proper actin dynamics in vivo. A spontaneous mouse mutant, corneal disease 1(corn1), is deficient for DSTN, which causes epithelial hyperproliferation and neovascularization in the cornea. Dstn(corn1) mice exhibit an actin dynamics defect in the cornea as evidenced by the formation of actin stress fibers in the epithelial cells. Previously, we observed a significant infiltration of leukocytes into the cornea of Dstn(corn1) mice as well as the upregulation of proinflammatory molecules. In this study, we sought to characterize this inflammatory condition and explore the physiological mechanism through which a loss of Dstn function leads to inflammation.Through immunofluorescent analyses, we observed a significant recruitment of neutrophils and macrophages to the Dstn(corn1) cornea, demonstrating that the innate immune system is spontaneously activated in this mutant. The inflammatory chemokine, CXCL5, was ectopically expressed in the corneal epithelial cells of Dstn(corn1) mice, and targeting of the receptor for this chemokine inhibited neutrophil recruitment. An inflammatory reaction was not observed in the cornea of allelic mutant strain, Dstn(corn1-2J), which has a milder defect in actin dynamics in the corneal epithelial cells.This study shows that severe defects in actin dynamics lead to an autoinflammatory condition that is mediated by the expression of CXC chemokines

The Elusive Word, theoria, and Political Science

創立八十周年記念特

Hirocracy as a Political Issue (The Origin of Aristotle\u27s Religious and Political Sciences) : Didactic History of Egyptian Politic

福島四郎教授還暦記念特

"Freedom of Conscience " and the Danish Source of the English Rule of Law : Related to the Moral Standbys for Our Country

伊沢孝平教授還暦記念特

What "tó tí ên eînai" Means to Me : in Aristotelian Political Philosophy

故岩崎卯ー教授追悼特

Orthodox Political Science as the Architectoni : A Study of the Post-quantum-theory Methodology

川上敬逸教授還暦記念特

Sakyamunii Buddhismo Recenti Democratiaeque : Virginibus Puerisque in Asia Orientis

植田重正教授還暦記念特

Chemotherapy with low-dose capecitabine as palliative treatment in a patient with metastatic breast cancer: a case report

Chemotherapeutic agents are rarely used for symptom management in patients under palliative care setting. This is because chemotherapeutic agents not only have limited efficacy in palliative treatment but are also known to exert severe adverse effects. We describe our experience with a patient with metastatic breast cancer who was successfully treated with low-dose capecitabine, without the development of any severe toxicities and with significant improvement in activities of daily living (ADL) and quality of life (QOL)