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Inhalation Toxicology
International Forum for Respiratory Research
Volume 20, 2008 - Issue 4
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Research Article

Effects of Particulate Matter on Cytokine Production In Vitro: A Comparative Analysis of Published Studies

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Pages 399-414 | Received 17 Sep 2007, Accepted 18 Nov 2007, Published online: 06 Oct 2008
 

Abstract

In recent years evidence has accumulated indicating that airborne particles cause adverse health effects. To understand the underlying mechanisms, a multitude of in vitro studies have been performed focusing on inflammatory responses, especially cytokine production. However, the diversity of studies renders it difficult to determine which results are consistent and which exposures most effective. The present review thus aimed to perform a comparative analysis of the available data. Forty-nine studies dealing with in vitro effects of particles on cytokine production in bronchial epithelial or related cells and monocytes/macrophages were included. Twenty-eight studies investigated epithelial cells and could be categorized according to specific combinations of exposure level and time, and 27 dealt with monocytes/macrophages. Eight studies provided further data using non-compatible exposure modes. The most common finding was that particles significantly induced cytokine production in both epithelial cells and monocytes/macrophages at concentrations of 50–100 μg/mL and exposure times of 9–24 h. The effects did not appear to be significantly different between cell or particle types. There were virtually no effects reported below 10 μ g/mL, but these levels were used in only a few studies. Thus, the available data demonstrate that cytokine measurements are sensitive enough to assess cell activation after particle exposure in vitro, yielding relatively consistent results across cell types. However, since the majority of data refers to high particle load compared to in vivo conditions, future studies should consider more sensitive assays, multivariate panels describing the cell's regulatory state, interactions between cell types, and second-line outcome measures that are close to clinically observed effects.

Abbreviations
A549,=

Type II human alveolar-like epithelial cells;

AA,=

Arachidonic acid;

AM,=

Alveolar monocyte;

AP-1,=

Activator protein-1;

CB,=

Carbon black (particles);

CL,=

Chemiluminescence;

COPD,=

Chronic Obstructive Pulmonary Disease;

COX-2,=

Cyclooxygenase-2;

DEP,=

Diesel exhaust particle;

EGF,=

Epidermal growth factor;

EGFR,=

Epidermal growth factor receptor;

EMSA,=

Electrophoretic mobility shift assay;

ERK,=

Extracellular signal-regulated kinase;

GM-CSF,=

Granulocyte-macrophage colony stimulating factor;

GGT,=

Gamma glutamyl transpeptidase;

HBEC,=

Human bronchial epithelial cells;

HNE,=

Human nasal epithelial cell;

HUVEC,=

Human vein endothelial cell;

ICAM-x,=

Intercellular adhesion molecule-x;

IFN-γ,=

Interferon-gamma;

I-κB,=

Inhibitor of Nuclear factor kappa B;

IL-x,=

Interleukin-x;

J774,=

Mouse monocyte cell line;

JNK,=

c-Jun N-terminal Kinase;

L132,=

Human epithelial lung cell line;

LDH,=

Lactate dehydrogenase;

LPS,=

Lipopolysaccharide;

μg/cm2,=

Microgram per square centimeter;

μg/m3,=

Microgram per cubic meter;

μg/mL,=

Microgram per milliliter;

MAPK,=

Mitogen-activated protein kinase;

MIP-x,=

Macrophage inflammatory protein-x;

mRNA,=

Messenger RNA;

NF-κB,=

Nuclear factor-kappa B;

NO,=

Nitric oxide;

NO2,=

Nitrite;

PGE2,=

Prostaglandin E2;

PMxy,=

Particulate matterxy;

RAS,=

Right angular scatter;

RNA,=

Ribonucleic acid;

ROFA,=

Residual oil fly ash;

ROS,=

Reactive oxygen species;

RPA,=

RNase protection assay;

SiO2,=

Silica dioxide;

TF,=

Tissue factor;

TiO2,=

Titanium dioxide;

TLR,=

Toll-like receptor;

TNF-α,=

Tumour necrosis factor-α;

tPA,=

Tissue plasminogen activator;

UFP,=

Ultrafine particulate matter

Abbreviations
A549,=

Type II human alveolar-like epithelial cells;

AA,=

Arachidonic acid;

AM,=

Alveolar monocyte;

AP-1,=

Activator protein-1;

CB,=

Carbon black (particles);

CL,=

Chemiluminescence;

COPD,=

Chronic Obstructive Pulmonary Disease;

COX-2,=

Cyclooxygenase-2;

DEP,=

Diesel exhaust particle;

EGF,=

Epidermal growth factor;

EGFR,=

Epidermal growth factor receptor;

EMSA,=

Electrophoretic mobility shift assay;

ERK,=

Extracellular signal-regulated kinase;

GM-CSF,=

Granulocyte-macrophage colony stimulating factor;

GGT,=

Gamma glutamyl transpeptidase;

HBEC,=

Human bronchial epithelial cells;

HNE,=

Human nasal epithelial cell;

HUVEC,=

Human vein endothelial cell;

ICAM-x,=

Intercellular adhesion molecule-x;

IFN-γ,=

Interferon-gamma;

I-κB,=

Inhibitor of Nuclear factor kappa B;

IL-x,=

Interleukin-x;

J774,=

Mouse monocyte cell line;

JNK,=

c-Jun N-terminal Kinase;

L132,=

Human epithelial lung cell line;

LDH,=

Lactate dehydrogenase;

LPS,=

Lipopolysaccharide;

μg/cm2,=

Microgram per square centimeter;

μg/m3,=

Microgram per cubic meter;

μg/mL,=

Microgram per milliliter;

MAPK,=

Mitogen-activated protein kinase;

MIP-x,=

Macrophage inflammatory protein-x;

mRNA,=

Messenger RNA;

NF-κB,=

Nuclear factor-kappa B;

NO,=

Nitric oxide;

NO2,=

Nitrite;

PGE2,=

Prostaglandin E2;

PMxy,=

Particulate matterxy;

RAS,=

Right angular scatter;

RNA,=

Ribonucleic acid;

ROFA,=

Residual oil fly ash;

ROS,=

Reactive oxygen species;

RPA,=

RNase protection assay;

SiO2,=

Silica dioxide;

TF,=

Tissue factor;

TiO2,=

Titanium dioxide;

TLR,=

Toll-like receptor;

TNF-α,=

Tumour necrosis factor-α;

tPA,=

Tissue plasminogen activator;

UFP,=

Ultrafine particulate matter

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