Inhaled particulate matter causes expression of nuclear factor (NF)-kappaB-related genes and oxidant-dependent NF-kappaB activation in vitro.
High levels of ambient air pollution are associated with exacerbation of asthma and respiratory morbidity, yet little is known concerning the mechanisms of inflammation and toxicity by components of inhaled particulate matter (PM). Brief inhalation of PM(2.5) (particles of an aerodynamic diameter of < 2.5 microns) (300 microg/m(3) air for 6 h followed by a period of 24 h in clean air) by either C3H/HeJ or C57/BL6 mice caused significant (P </= 0.05) increases in steady-state messenger RNA (mRNA) levels of a number of nuclear factor (NF)-kappaB-associated and/ or -regulated genes, including tumor necrosis factor-alpha and -beta, interleukin-6, interferon-gamma, and transforming growth factor-beta. Lung mRNA levels of lymphotoxin-beta and macrophage migration inhibitory factor were unchanged. In murine C10 alveolar cells and an NF-kappaB-luciferase reporter cell line, exposure to PM(2.5) at noncytotoxic concentrations resulted in increases in transcriptional activation of NF-kappaB-dependent gene expression which were inhibited in the presence of catalase. Early and persistent increases in intracellular oxidants, as measured by flow cytometry and cell imaging using the oxidant probe 2'-7'-dichlorofluoroscin diacetate, were observed in epithelial cells exposed to PM(2.5) and ultrafine carbon black particles. Studies here are the first to show NF-kappaB-related inflammatory and cytokine gene expression after inhalation of PM(2.5) and oxidant-dependent induction of NF-kappaB activity by PM(2.5) in pulmonary epithelial cells.
Shukla
A
A
Departments of Pathology and Biostatistics, University of Vermont, Burlington, Vermont 05405, USA.
Timblin
C
C
BeruBe
K
K
Gordon
T
T
McKinney
W
W
Driscoll
K
K
Vacek
P
P
Mossman
B T
BT
D000393:Air Pollutants / Q000494:pharmacology*; D000818:Animals; D002244:Carbon / Q000494:pharmacology; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005452:Fluoresceins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D019570:Inhalation Exposure; D007371:Interferon-gamma / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000235:genetics; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism / Q000502:physiology*; D010316:Particle Size; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000393:Air Pollutants; D005452:Fluoresceins; D015850:Interleukin-6; D008233:Lymphotoxin-alpha; D016328:NF-kappa B; D016877:Oxidants; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C029569:diacetyldichlorofluorescein; D002244:Carbon; D007371:Interferon-gamma; D004247:DNA