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Tumor necrosis factor-α mediates interactions between macrophages and epithelial cells underlying proinflammatory gene expression induced by particulate matter.
Toxicology. 2012 Sep 28; 299(2-3):125-32.T

Abstract

Ambient particulate matter (PM) exposure is known to have adverse effects on respiratory health, but the underlying mechanisms remain obscure. We tested the hypothesis that macrophages and epithelial cells synergize to produce maximal cytokine release in response to PM exposure, thereby promoting inflammatory responses. We developed a co-culture model using MLE-12 (mouse lung epithelial) cells and RAW 264.7 (mouse monocyte/macrophage) cells. MLE-12 cells produced KC (Cxcl1) but not tumor necrosis factor-α (TNF), and KC was upregulated only at high levels of urban particulate matter (UPM; NIST 1648a). RAW 264.7 cells produced TNF but not KC, and TNF production was increased by treatment with UPM. In contrast, KC production was upregulated by co-culture of MLE-12 and RAW 264.7 cells, and it was further increased by treatment with a concentration of UPM that had no effect on MLE-12 cells alone. Multiplex cytokine assay revealed a similar pattern of synergistic production of MIG (Cxcl9) and IP-10 (Cxcl10) in co-cultures in response to UPM. TNF was implicated as mediating the synergistic increase in KC production because TNF upregulated KC production in MLE-12 cells, and UPM-induced KC production in co-cultures could be inhibited by a TNF blocking antibody. Intratracheal instillation of UPM into both wild-type and TNF receptor knockout mice resulted in increased TNF production in lavage fluid and increased TNF mRNA expression in cells recovered from lavage fluid. Additionally, UPM instillation into wild-type mice resulted in increased neutrophils and KC in lavage fluid, and these were inhibited in UPM-exposed TNF receptor knockout mice. These results are consistent with a model in which PM activates TNF production in macrophages which in turn stimulates epithelial cells to produce proinflammatory cytokines such as KC. The findings suggest a potential mechanism by which inhaled PM induces inflammation in the lung.

Authors+Show Affiliations

Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY 40202, United States.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22634322

Citation

Musah, Sadiatu, et al. "Tumor Necrosis Factor-α Mediates Interactions Between Macrophages and Epithelial Cells Underlying Proinflammatory Gene Expression Induced By Particulate Matter." Toxicology, vol. 299, no. 2-3, 2012, pp. 125-32.
Musah S, DeJarnett N, Hoyle GW. Tumor necrosis factor-α mediates interactions between macrophages and epithelial cells underlying proinflammatory gene expression induced by particulate matter. Toxicology. 2012;299(2-3):125-32.
Musah, S., DeJarnett, N., & Hoyle, G. W. (2012). Tumor necrosis factor-α mediates interactions between macrophages and epithelial cells underlying proinflammatory gene expression induced by particulate matter. Toxicology, 299(2-3), 125-32. https://doi.org/10.1016/j.tox.2012.05.014
Musah S, DeJarnett N, Hoyle GW. Tumor Necrosis Factor-α Mediates Interactions Between Macrophages and Epithelial Cells Underlying Proinflammatory Gene Expression Induced By Particulate Matter. Toxicology. 2012 Sep 28;299(2-3):125-32. PubMed PMID: 22634322.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tumor necrosis factor-α mediates interactions between macrophages and epithelial cells underlying proinflammatory gene expression induced by particulate matter. AU - Musah,Sadiatu, AU - DeJarnett,Natasha, AU - Hoyle,Gary W, Y1 - 2012/05/23/ PY - 2012/03/16/received PY - 2012/05/09/revised PY - 2012/05/16/accepted PY - 2012/5/29/entrez PY - 2012/5/29/pubmed PY - 2012/12/10/medline SP - 125 EP - 32 JF - Toxicology JO - Toxicology VL - 299 IS - 2-3 N2 - Ambient particulate matter (PM) exposure is known to have adverse effects on respiratory health, but the underlying mechanisms remain obscure. We tested the hypothesis that macrophages and epithelial cells synergize to produce maximal cytokine release in response to PM exposure, thereby promoting inflammatory responses. We developed a co-culture model using MLE-12 (mouse lung epithelial) cells and RAW 264.7 (mouse monocyte/macrophage) cells. MLE-12 cells produced KC (Cxcl1) but not tumor necrosis factor-α (TNF), and KC was upregulated only at high levels of urban particulate matter (UPM; NIST 1648a). RAW 264.7 cells produced TNF but not KC, and TNF production was increased by treatment with UPM. In contrast, KC production was upregulated by co-culture of MLE-12 and RAW 264.7 cells, and it was further increased by treatment with a concentration of UPM that had no effect on MLE-12 cells alone. Multiplex cytokine assay revealed a similar pattern of synergistic production of MIG (Cxcl9) and IP-10 (Cxcl10) in co-cultures in response to UPM. TNF was implicated as mediating the synergistic increase in KC production because TNF upregulated KC production in MLE-12 cells, and UPM-induced KC production in co-cultures could be inhibited by a TNF blocking antibody. Intratracheal instillation of UPM into both wild-type and TNF receptor knockout mice resulted in increased TNF production in lavage fluid and increased TNF mRNA expression in cells recovered from lavage fluid. Additionally, UPM instillation into wild-type mice resulted in increased neutrophils and KC in lavage fluid, and these were inhibited in UPM-exposed TNF receptor knockout mice. These results are consistent with a model in which PM activates TNF production in macrophages which in turn stimulates epithelial cells to produce proinflammatory cytokines such as KC. The findings suggest a potential mechanism by which inhaled PM induces inflammation in the lung. SN - 1879-3185 UR - https://www.unboundmedicine.com/medline/citation/22634322/Tumor_necrosis_factor_α_mediates_interactions_between_macrophages_and_epithelial_cells_underlying_proinflammatory_gene_expression_induced_by_particulate_matter_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300-483X(12)00170-9 DB - PRIME DP - Unbound Medicine ER -