TNF alpha and MIP-2: role in particle-induced inflammation and regulation by oxidative stress

The cytokine tumor necrosis factor alpha (TNF alpha) plays a critical role in particle-induced inflammation in the lung. TNF alpha production by macro phage can be stimulated by a variety of noxious particles and initiate a ca scade of responses involving adhesion molecule expression and production of chemotactic cytokines which ultimately result in the infiltration of infla mmatory cells to site of infection or tissue injury in the respiratory trac t. Regarding chemotactic cytokines, TNF alpha is a potent agonist of chemok ine expression in both immune and non-immune cells (e.g. epithelial cells, fibroblasts). The chemokine macrophage inflammatory protein-2 (MIP-2) plays a major role in mediating the neutrophilic inflammatory response of the ro dent lung to particles such as quartz, crocidolite asbestos, as well as hig h doses of other relative innocuous dusts such as titanium dioxide. The doc umented sources of MIP-2 in the rodent lung after particle exposure include macrophages as well as epithelial cells. Recent studies indicate that expr ession of the MIP-2 gene in rat lung epithelial cells is dependent on the t ranscription factor NF kappa B and is regulated, in part, by oxidative stre ss induced by particle exposure. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.