Diesel Exhaust Particles Activate p38 MAP Kinase to Produce Interleukin 8 and RANTES by Human Bronchial Epithelial Cells and <i>N</i>-Acetylcysteine  Attenuates p38 MAP Kinase Activation

Hashimoto, Shigeo; Gon, Yasuhiro; Takeshita, Ikuko; Matsumoto, Ken; Jibiki, Itsuro; Takizawa, Hajime; Kudoh, Shoji; Horie, Takashi

doi:10.1164/ajrccm.161.1.9904110

Cited by 127 publications

(92 citation statements)

References 32 publications

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“…In the literature, the effect of NAC on p38 MAPK is cell type-dependent; in human bronchial epithelial cells, NAC did not affect influenza virus infection-induced increases in p38 MAPK phosphorylation [17], but in other cell types such as in human pulmonary vascular endothelial cells, there is some evidence that NAC affects the activation of p38 MAPK [14,18].…”

Section: Discussionmentioning

confidence: 98%

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N‐acetylcysteine reduces chemokine releaseviainhibition of p38 MAPK in human airway smooth muscle cells

Wuyts¹,

Vanaudenaerde²,

Dupont³

et al. 2003

Eur Respir J

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Reactive oxygen species are involved in the activation of several mitogenactivated protein kinases (MAPKs), key-players in the production of several cytokines. Therefore the current study investigated whether N-acetylcysteine (NAC), an antioxidative agent, inhibits the interleukin (IL)-1b-induced expression and production of eotaxin and monocyte chemotactic protein (MCP)-1 in human airway smooth muscle cells (HASMC).NAC (10 mM) decreased the expression of eotaxin and MCP-1, by 46¡11% (n=7) and 87¡4% (n=6), respectively; the eotaxin release was inhibited by 75¡5% (n=7), whereas the MCP-1 release was decreased by 69¡4% (n=10). NAC (1 mM) also decreased the IL-1b-induced activation of p38 MAPK.Compared with unstimulated cells, a four-fold increase in 8-isoprostane production in IL-1b-stimulated HASMC was observed, which could be inhibited by NAC in a concentration-dependent way, with a maximum inhibition of 39¡12% with 1 mM NAC.The present study demonstrated that N-acetylcysteine inhibits the interleukin-1b-induced eotaxin and monocyte chemotactic protein 1 expression and production due to a decreased activation of p38 mitogen-activated protein kinase. This study has also shown that N-acetylcysteine decreases the interleukin-1b-induced production of reactive oxygen species, as suggested by a reduction in the 8-isoprostane production.

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Section: Discussionmentioning

confidence: 98%

“…Indeed, ROS seem to be involved in the activation of p38 MAPKs in different cell types, such as vascular smooth muscle cells [11,26,27] and bronchial epithelial cells, stimulated with diesel exhaust particles [18].…”

Section: Discussionmentioning

confidence: 99%

N‐acetylcysteine reduces chemokine releaseviainhibition of p38 MAPK in human airway smooth muscle cells

Wuyts¹,

Vanaudenaerde²,

Dupont³

et al. 2003

Eur Respir J

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“…The observation that these sterile stimuli all signal through the IL-1RI could suggest that pollutants stimulate lung inflammatory responses through a common IL-1RI-dependent mechanism (5). However, DEP inhalation can also induce chemokines, like KC, directly from the epithelium (22). Probably, this explains the limited, but increased, pulmonary inflammation in DEP-exposed IL-1RI KO mice when compared with saline-exposed IL-1RI KO mice.…”

Section: Discussionmentioning

confidence: 99%

NLRP3/Caspase-1–Independent IL-1β Production Mediates Diesel Exhaust Particle-Induced Pulmonary Inflammation

Provoost

Maes

Pauwels

et al. 2011

The Journal of Immunology

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Inhalation of diesel exhaust particles (DEP) induces an inflammatory reaction in the lung; however, the mechanisms are largely unclear. IL-1β/IL-1RI signaling is crucial in several lung inflammatory responses. Typically, caspase-1 is activated within the NLRP3 inflammasome that recognizes several damage-associated molecular patterns, which results in cleavage of pro–IL-1β into mature IL-1β. In this study, we hypothesized that the NLRP3/caspase-1/IL-1β pathway is critical in DEP-induced lung inflammation. Upon DEP exposure, IL-1RI knockout mice had reduced pulmonary inflammation compared with wild-type mice. Similarly, treatment with rIL-1R antagonist (anakinra) and IL-1β neutralization impaired the DEP-induced lung inflammatory response. Upon DEP exposure, NLRP3 and caspase-1 knockout mice, however, showed similar IL-1β levels and comparable pulmonary inflammation compared with wild-type mice. In conclusion, these data show that the DEP-induced pulmonary inflammation acts through the IL-1β/IL-1RI axis. In addition, DEP initiates inflammation independent of the classical NLRP3/caspase-1 pathway, suggesting that other proteases might be involved.

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“…Adsorbed organic compounds have been implicated in many of the systemic and molecular responses of respiratory system cells exposed to diesel exhaust particles (3)(4)(5)(6). Studies with residual oil fly ash (ROFA) particles have demonstrated a role for particleassociated metals in inducing inflammatory responses in respiratory cells (7,8).…”

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confidence: 99%

Combustion products of 1,3-butadiene are cytotoxic and genotoxic to human bronchial epithelial cells.

Catallo

Kennedy

Henk

et al. 2001

Environ Health Perspect

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Adverse health effects of airborne toxicants, especially small respirable particles and their associated adsorbed chemicals, are of growing concern to health professionals, governmental agencies, and the general public. Areas rich in petrochemical processing facilities (e.g., eastern Texas and southern California) chronically have poor air quality. Atmospheric releases of products of incomplete combustion (e.g., soot) from these facilities are not subject to rigorous regulatory enforcement. Although soot can include respirable particles and carcinogens, the toxicologic and epidemiologic consequences of exposure to environmentally relevant complex soots have not been well investigated. Here we continue our physico-chemical analysis of butadiene soot and report effects of exposure to this soot on putative targets, normal human bronchial epithelial (NHBE) cells. We examined organic extracts of butadiene soot by gas chromatography-mass spectrometry (GC-MS), probe distillation MS, and liquid chromatography (LC)-MS-MS. Hundreds of aromatic hydrocarbons and polycyclic aromatic hydrocarbons with molecular mass as high as 1,000 atomic mass units were detected, including known and suspected human carcinogens (e.g., benzo(a)pyrene). Butadiene soot particles also had strong, solid-state free-radical character in electron spin resonance analysis. Spin-trapping studies indicated that fresh butadiene soot in a buffered aqueous solution containing dimethylsulfoxide (DMSO) oxidized the DMSO, leading to CH(3)* radical formation. Butadiene soot DMSO extract (BSDE)-exposed NHBE cells displayed extranuclear fluorescence within 4 hr of exposure. BSDE was cytotoxic to > 20% of the cells at 72 hr. Morphologic alterations, including cell swelling and membrane blebbing, were apparent within 24 hr of exposure. These alterations are characteristic of oncosis, an ischemia-induced form of cell death. BSDE treatment also produced significant genotoxicity, as indicated by binucleated cell formation. The combination of moderate cytotoxicity and genotoxicity, as occurred here, can be pro-carcinogenic.

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Diesel Exhaust Particles Activate p38 MAP Kinase to Produce Interleukin 8 and RANTES by Human Bronchial Epithelial Cells and N-Acetylcysteine Attenuates p38 MAP Kinase Activation

Cited by 127 publications

References 32 publications

N‐acetylcysteine reduces chemokine releaseviainhibition of p38 MAPK in human airway smooth muscle cells

N‐acetylcysteine reduces chemokine releaseviainhibition of p38 MAPK in human airway smooth muscle cells

NLRP3/Caspase-1–Independent IL-1β Production Mediates Diesel Exhaust Particle-Induced Pulmonary Inflammation

Combustion products of 1,3-butadiene are cytotoxic and genotoxic to human bronchial epithelial cells.

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