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

Our plain-English summary of TNFalpha and MIP-2: role in particle-induced inflammation and regulation by oxidative stress, by K.E. Driscoll (Toxicology Letters, 2000).

The study

• Author: K.E. Driscoll
• Journal: Toxicology Letters
• Published: 2000;112-113:177-83
• Type of article: Review
• Cited by: 141 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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.

In plain English

This article was a single-author review of research on two signaling proteins, TNF-alpha and MIP-2, and their role in dust-induced lung inflammation. Most of the work came from earlier laboratory studies in rats and rat lung cells, many by the author's group. In test-tube studies, quartz and the asbestos fibers crocidolite and chrysotile strongly stimulated alveolar macrophages (lung immune cells) to release TNF-alpha. The author described titanium dioxide, aluminum oxide and latex beads as not potent stimulators. In rats, an antibody blocking TNF-alpha reduced the influx of white blood cells called neutrophils after quartz or titanium dioxide. Blocking MIP-2 reduced neutrophil influx after quartz by 60%. Crocidolite asbestos, but not titanium dioxide or MMVF-10 glass fibers, triggered MIP-2 in rat lung lining cells. An antioxidant reduced the crocidolite response. The author concluded that a material's ability to cause oxidative stress in lung cells is one way it can switch on inflammatory genes. The main experiments concerned short-term inflammation in rats and cultured cells. The review also cited reports of increased macrophage TNF-alpha in people with asbestosis or coal workers' pneumoconiosis.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of laboratory research (mostly in vitro cell studies and rat experiments, many from the author's own group)
• Who was studied: Rats (including F344 rats), rat and human alveolar macrophages, and rat lung epithelial cells (the RLE-6TN cell line and primary cultures), as described in the studies reviewed
• Exposure: Particles including quartz, crocidolite asbestos, chrysotile asbestos, coal dust, titanium dioxide, aluminum oxide, latex beads and MMVF-10 glass fibers, given to cells in culture or to rats by inhalation or instillation into the airway
• Main results:
  • In test-tube studies, quartz, crocidolite and chrysotile were potent stimulators of TNF-alpha release by alveolar macrophages. The author described titanium dioxide, aluminum oxide and latex beads as not potent stimulators. Table 1 is scrambled by OCR but appears to score titanium dioxide as equivocal (+/–) in human macrophages.
  • In rats, pretreatment with an anti-TNF-alpha antibody reduced neutrophil recruitment to the lungs after quartz or titanium dioxide exposure. The figure legend reports groups of six F344 rats and a statistically significant difference (p less than 0.01).
  • In rats given quartz, pretreatment with antibody to MIP-2 reduced neutrophil recruitment by 60%. The figure legend gives 3 rats per treatment.
  • In rats exposed to quartz, epithelial cells in the terminal bronchioles were the main cells expressing MIP-2 messenger RNA within 2 hours. Lung macrophages and newly recruited neutrophils expressed MIP-2 at later times.
  • Crocidolite asbestos induced MIP-2 expression in rat lung epithelial cells. Titanium dioxide and MMVF-10 glass fibers did not.
  • In RLE-6TN rat lung epithelial cells, the antioxidant TMTU significantly reduced crocidolite-induced MIP-2 gene expression. Nuclear translocation of the transcription factor NFkB was also reduced.
  • The review cited earlier reports that macrophage TNF-alpha production is increased in asbestosis patients.
  • The same sentence, continued elsewhere in the OCR text, extends this to individuals with coal workers' pneumoconiosis.
• The authors' conclusion: The author concluded that a material's ability to exert oxidative stress on lung cells represents a mechanism for upregulating inflammatory cytokine genes and initiating an inflammatory response.

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, Oxidative Stress, Cytokine, Necrosis, Macrophage, Fibroblast, Crocidolite.

Related studies

• Effect of N-acetylcysteine supplementation on oxidative stress status and alveolar inflammation in people exposed to asbestos: a double-blind, randomized clinical trial — H. Alfonso, P. Franklin, et al. (2015)
• The latent form of TGFbeta(1) is induced by TNFalpha through an ERK specific pathway and is activated by asbestos-derived reactive oxygen species in vitro and in vivo — D.E. Sullivan, M. Ferris, et al. (2008)
• The role of iron in Libby amphibole-induced acute lung injury and inflammation — J.H. Shannahan, A.J. Ghio, et al. (2011)
• Role of transcription factor NF-kappaB in asbestos-induced TNFalpha response from macrophages — N. Cheng, X. Shi, et al. (1999)
• Oxidative and cytotoxic stress induced by inorganic granular and fibrous particles — S. Helmig, D. Walter, et al. (2018)
• Asbestos fibers and silica particles stimulate rat alveolar macrophages to release tumor necrosis factor. Autoregulatory role of leukotriene B4 — C.M. Dubois, E. Bissonnette, et al. (1989)

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