TNFalpha and MIP-2: role in particle-induced inflammation and regulation by oxidative stress.
The cytokine tumor necrosis factor alpha (TNFalpha) plays a critical role in particle-induced inflammation in the lung. TNFalpha production by macrophage can be stimulated by a variety of noxious particles and initiate a cascade of responses involving adhesion molecule expression and production of chemotactic cytokines which ultimately result in the infiltration of inflammatory cells to site of infection or tissue injury in the respiratory tract. Regarding chemotactic cytokines, TNFalpha is a potent agonist of chemokine 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 rodent lung to particles such as quartz, crocidolite asbestos, as well as high doses of other relative innocuous dusts such as titanium dioxide. The documented sources of MIP-2 in the rodent lung after particle exposure include macrophages as well as epithelial cells. Recent studies indicate that expression of the MIP-2 gene in rat lung epithelial cells is dependent on the transcription factor NFkappaB and is regulated, in part, by oxidative stress induced by particle exposure.
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Procter and Gamble Pharmaceuticals, Health Care Research Center, 8700 Mason Montgomery Road, Mason, OH, USA.
D000818:Animals; D004391:Dust; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000502:physiology*; D018384:Oxidative Stress; D011650:Pulmonary Alveoli / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D004391:Dust; D019402:Macrophage Inflammatory Proteins; D014409:Tumor Necrosis Factor-alpha