Recent advances in particulate-induced pulmonary fibrosis; for the application of possible strategy experimentally and clinically.
Chronic interstitial lung diseases including pneumoconiosis have pathological characteristics which alter the lung structure and function consequent to the accumulation and activation of inflammatory cells in the lower respiratory tract. These activated cells usually secrete the inflammatory and fibrogenic mediators. Of the diffuse parenchymal lung diseases, the majority have no known etiology and idiopathic pulmonary fibrosis (IPF) is the diagnosis most frequently encountered by clinicians. Pathogenic similarities between pneumoconiosis and IPF provide a strong basis for hypothesizing that environmental agents may cause IPF. Many case-control studies have been published that provide further evidence for a number of associations between occupational and environmental exposures and IPF. Such reports support a strong evidence that IPF may be a heterogenous disorder associated with a number of environmental exposures. As a model of lung fibrosis, experimental pneumoconiosis is giving us a great information because crystalline silica is probably one of the most typical agent producing pulmonary fibrosis and the severity of its health effects and the widespread nature of exposure have been long recognized. Many papers provide evidence that particles have the potential to cause stimulation of phagocytes to release oxidants and such oxidative stress is believed to be a major factor in pulmonary inflammation followed by fibrotic change. Many kinds of cellular mediators are recognized as a implicating factor in this process including cell-to-cell interaction, enzymes, cytokines, arachidonic acid derivatives et al. Treatment of pneumoconiosis is an attractive and interesting topic. But, the mechanism of pathogenesis of pneumoconiosis is not thoroughly understood yet. Also, whether the process of fibrosis formation be retarded or not is questionable with some therapeutic trial. Therefore, a sensitive biomarker which is possible to estimate the pathological pathway in pneumoconiosis is needed. Our laboratory has studied particulate-induced pulmonary reaction for two decades consistently. This review will focus on signal transduction pathway involved in oxidative stress and some inhibitory agents with pleiotropic mechanism in pulmonary fibrosis. I will also introduce some data of animal studies with multidrug regimen as well.
Kim
K A
KA
Department of Occupational and Environmental Medicine, St Mary's Hospital, The Catholic University of Korea, Seoul.
Park
C Y
CY
Lim
Y
Y
Lee
K H
KH
D000305:Adrenal Cortex Hormones / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001798:Blood Proteins / Q000494:pharmacology / Q000627:therapeutic use; D002614:Chelating Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011658:Pulmonary Fibrosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012822:Silicon Dioxide / Q000009:adverse effects
D000305:Adrenal Cortex Hormones; D000975:Antioxidants; D001798:Blood Proteins; D002614:Chelating Agents; D016207:Cytokines; C400481:PLIalpha; D017382:Reactive Oxygen Species; D012822:Silicon Dioxide; D003676:Deferoxamine