Metallothionein as an Anti-Inflammatory Mediator

The integration of knowledge concerning the regulation of MT, a highly conserved, low molecular weight, cystein-rich metalloprotein, on its proposed functions is necessary to clarify how MT affects cellular processes. MT expression is induced/enhanced in various tissues by a number of physiological mediators. The cellular accumulation of MT depends on the availability of cellular zinc derived from the diet. MT modulates the binding and exchange/transport of heavy metals such as zinc, cadmium, or copper under physiological conditions and cytoprotection from their toxicities, and the release of gaseous mediators such as hydroxyl radicals or nitric oxide. In addition, MT reportedly affects a number of cellular processes, such as gene expression, apoptosis, proliferation, and differentiation. Given the genetic approach, the apparently healthy status of MT-deficient mice argues against an essential biological role for MT; however, this molecule may be critical in cells/tissues/organs in times of stress, since MT expression is also evoked/enhanced by various stresses. In particular, because metallothionein (MT) is induced by inflammatory stress, its roles in inflammation are implied. Also, MT expression in various organs/tissues can be enhanced by inflammatory stimuli, implicating in inflammatory diseases. In this paper, we review the role of MT of various inflammatory conditions

Impact of Diesel Exhaust Particles on Th2 Response in the Lung in Asthmatic Mice

Although it has been accepted that pulmonary exposure to diesel exhaust particles (DEP), representative constituents in particulate matter of mass median aerodynamic diameter < or 2.5 µm (PM2.5), exacerbates murine allergic asthma, the in vivo effects of DEP on their cellular events in the context of allergen-specific Th response have never been examined. The aim of this study is to elucidate whether in vivo repetitive exposure to DEP combined with allergen (ovalbumin) facilitate allergen-specific Th response in the lung using a simple ex vivo assay system. As a result, repetitive pulmonary exposure to DEP in vivo, if combined with allergen, amplifies ex vivo allergen-specific Th2 response in the lung compared to that to allergen alone, characterized by high levels of interleukin (IL)-4 and IL-5. The result suggests that in asthmatic subjects, DEP promote Th2-prone milieu in the lung, which additively/synergistically augment asthma pathophysiology in vivo

Extensive Analysis of Elastase-Induced Pulmonary Emphysema in Rats: ALP in the Lung, a New Biomarker for Disease Progression?

It is accepted that pulmonary exposure of rodents to porcine pancreatic elastase (ELT) induces lesions that morphologically resemble human emphysema. Nonetheless, extensive analysis of this model has rarely been conducted. The present study was designed to extensively examine the effects of ELT on lung inflammation, cell damage, emphysematous change, and cholinergic reactivity in rats. Intratracheal administration of two doses of ELT induced 1) a proinflammatory response in the lung that was characterized by significant infiltration of macrophages and an increased level of interleukin-1β in lung homogenates, 2) lung cell damage as indicated by higher levels of total protein, lactate dehydrogenase, and alkaline phosphatase (ALP) in lung homogenates, 3) emphysema-related morphological changes including airspace enlargement and progressive destruction of alveolar wall structures, and 4) airway responsiveness to methacholine including an augmented Rn value. In addition, ELT at a high dose was more effective than that at a low dose. This is the novel study to extensively analyze ELT-induced lung emphysema, and the analysis might be applied to future investigations that evaluate new therapeutic agents or risk factors for pulmonary emphysema. In particular, ALP in lung homogenates might be a new biomarker for the disease progression/exacerbation