Diesel fumes make polyps grow and aggravate AERDs

[Guest guest]

Diesel exhaust particles (DEP) induce a Th2 dominance (Th2 stands for lymphocyte

T

helper 2, a subset of blood cells involved in immunity), so this aggravates

asthma and

AERDs, which are Th2-dominant diseases.

Also, DEP upregulate eotaxin, a cell signaling molecule which summons

eosinophils, a

subset of blood cells of which most polyps are made of.

N-acetyl-cysteine (NAC), a mucus breaker sold as Mucomyst, Fluimucil etc, may

help.

The following articles are about diesel, but who knows if super gasoline doesn't

have the

same effect?

So, avoid being caught in traffic jams (but if you are in one, it already means

you can't

avoid them)...

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J Immunol. 2005 Feb 15;174(4):2412-9. Links

Cellular basis of the role of diesel exhaust particles in inducing Th2-dominant

response.Ohtani T, Nakagawa S, Kurosawa M, Mizuashi M, Ozawa M, Aiba S.

Department of Dermatology, Tohoku University Graduate School of Medicine,

Sendai,

Japan.

There is growing evidence that diesel exhaust particles (DEP) can induce

allergic diseases

with increased IgE production and preferential activation of Th2 cells. To

clarify the

cellular basis of the role of DEP in the induction of Th2-dominant responses, we

examined

the effects of DEP on the cytokine production by T cells stimulated with

anti-CD3/CD28

Ab and on that by monocyte-derived dendritic cells (MoDCs) stimulated with CD40L

and/

or IFN-gamma. We examined IFN-gamma, IL-4, IL-5, IL-8, and IL-10 produced by T

cells

and TNF-alpha, IL-1beta, IL-10, and IL-12 produced by MoDCs using real-time PCR

analysis or by ELISA. To highlight the effects of DEP, we compared the effects

of DEP with

those of dexamethasone (DEX) and cyclosporin A (CyA). DEP significantly

suppressed IFN-

gamma mRNA expression and protein production, while it did not affect IL-4 or

IL-5

mRNA expression or protein production. The suppressive effect on IFN-gamma mRNA

expression was more potent than that of DEX and comparable at 30 mug/ml with

10(-7) M

CyA. The suppressive effect on IFN-gamma production was also more potent than

that of

either DEX or CyA. DEP suppressed IL-12p40 and IL-12p35 mRNA expression and IL

-12p40 and IL-12p70 production by MoDCs, while it augmented IL-1beta mRNA

expression. Finally, by using a thiol antioxidant, N-acetyl cysteine, we found

that the

suppression of IFN-gamma production by DEP-treated T cells was mediated by

oxidative

stress. These data revealed a unique characteristic of DEP, namely that they

induce a Th2

cytokine milieu in both T cells and dendritic cells.

Am J Physiol Lung Cell Mol Physiol. 2003 Jun;284(6):L1055-62. Epub 2003 Feb 7.

Links

Diesel exhaust particles upregulate eotaxin gene expression in human bronchial

epithelial

cells via nuclear factor-kappa B-dependent pathway.Takizawa H, Abe S, Okazaki H,

Kohyama T, Sugawara I, Saito Y, Ohtoshi T, Kawasaki S, Desaki M, Nakahara K,

Yamamoto

K, Matsushima K, Tanaka M, Sagai M, Kudoh S.

Departments of Laboratory Medicine and Respiratory Medicine, Graduate School of

Medicine, University of Tokyo, Tokyo 113-8655, Japan.

takizawa-phy@...

Fine particles derived from diesel engines, diesel exhaust particles (DEP), have

been shown

to augment gene expression of several inflammatory cytokines in human airway

epithelial

cells in vitro. However, it remains unclear whether or not DEP have any effect

on the

expression and production of eotaxin, an important chemokine involved in

eosinophil

recruitment into the airways. We studied the effects of DEP by using a

conventional

suspended DEP and by a recently established in vitro cell exposure system to

diesel

exhaust (Abe S, Takizawa H, Sugawara I, and Kudoh S, Am J Respir Cell Mol Biol

22: 296

-303, 2000). DEP showed a dose-dependent stimulatory effect on eotaxin

production by

normal human peripheral airway epithelial cells as well as by bronchial

epithelial cell line

BET-1A as assessed by specific ELISA. mRNA levels increased by DEP were shown by

RT-

PCR. DEP showed an additive effect on IL-13-stimulated eotaxin expression. DEP

induced

NF-kappaB activation by EMSA as previously reported but did not induce signal

transducer

and activator of transcription (STAT) 6 activation according to Western blot

analysis.

Finally, antioxidant agents (N-acetyl cysteine and pyrrolidine dithiocarbamate),

which

inhibited NF-kappaB activation but failed to affect STAT6 activation, almost

completely

attenuated DEP-induced eotaxin production, whereas these agents failed to

attenuate IL

-13-induced eotaxin production. These findings suggested that DEP stimulated

eotaxin

gene expression via NF-kappaB-dependent, but STAT6-independent, pathways.

J Toxicol Environ Health A. 2005 Sep;68(17-18):1537-55. Links

Motorcycle exhaust particles induce IL-8 production through NF-kappaB activation

in

human airway epithelial cells.Lee CC, Cheng YW, Kang JJ. Institute of

Toxicology, College

of Medicine, National Taiwan University, Taiwan, Republic of China.

Motorcycle exhaust particles (MEP) are among the major air pollutants,

especially in urban

area of Taiwan. In our previous study, data showed that MEP induce

proinflammatory and

proallergic response profiles in BALB/c mice. Effects of MEP on interleukin

(IL)-8

production in A549 human airway epithelial cells were further investigated in

this study. It

was found that MEP enhanced IL-8 protein and mRNA expression in human epithelial

cells.

Pretreatment with an NF-kappaB inhibitor (1 mM PDTC), extracellular

signal-regulated

kinase (ERK) inhibitor (50 microM PD98059), JNK inhibitor (25 microM SP600125),

p38

inhibitor (2 microM SB203580), and three antioxidants (500 U/ml superoxide

dismutase

[sOD], 50 microM vitamin E, 10 mMN-acetylcysteine [NAC]) attenuated the

MEP-induced

increase in IL-8 production. Through further, direct detection of nuclear factor

(NF)-

kappaB activation in epithelial cells using immunoblotting of nuclear p65 and

NF-kappaB

reporter assay, data showed that MEP induced nuclear translocation of p65 and

enhancement of NF-kappaB luciferase gene expression. MEP also induced activation

of

ERK, JNK, and p38 signaling pathways and produced an increase of oxidative

stress in

A549 cells. By using mitogen-activated protein kinase (MAPK) inhibitors and

antioxidant, it

was demonstrated that ERK inhibitor, JNK inhibitor, and antioxidants but not p38

inhibitor

attenuated the MEP-induced increase in NF-kappaB reporter activity. In

conclusion,

evidence shows that filter-trapped particles emitted from unleaded

gasoline-fueled, two-

stroke motorcycle engines induce an increase in IL-8 production by activation of

NF-

kappaB in human airway epithelial cells.

Eur Respir J. 2006 Apr;27(4):705-13. Epub 2006 Feb 2. Links

Comment in: Eur Respir J. 2006 Apr;27(4):667-8.

Regulation of human lung epithelial cell numbers by diesel exhaust particles.

Bayram H, Ito K, Issa R, Ito M, Sukkar M, Chung KF. Thoracic Medicine, National

Heart and

Lung Institute, Imperial College, London SW3 6LY, UK.

Particulate air pollution is associated with respiratory morbidity and has

cytotoxic and

pro-inflammatory effects. The effects of diesel exhaust particles (DEP) on

proliferation and

apoptosis of A549 lung epithelial cells were examined. When deprived of serum

(serum

starvation), epithelial cell numbers fell, but DEP (5-200 microg.mL-1) prevented

this.

Using flow cytometric analysis of propidium iodide (PI) staining, DEP (10

microg.mL-1)

increased cells in the S phase of cell cycle from 12.85 to 18.75% after 48 h,

reversing

serum starvation-induced G0/1 arrest. DEP also reduced the increase in apoptotic

cells, as

defined by double expression of annexin V/PI, observed after serum starvation

(from

28.35 to 15.46%). The antioxidants, N-acetylcysteine (NAC; 33 mM) and AEOL10113

(10

-100 microM), the N-terminal c-jun kinase inhibitor, SP600125 (33 microM), and

nuclear

factor-kappaB inhibitor, SN50 (33 microM), inhibited DEP-induced cell number

increase.

NAC inhibited DEP-induced reduction of G0/1 and increase in cells in the S and

G2/M

phases. Expression of p21CIP1/WAF1 mRNA and protein seen with serum starvation

was

reduced by DEP. In conclusion, diesel exhaust particles prevented serum

starvation-led

decreases in A549 epithelial cells by inducing cell cycle progression and

preventing

apoptosis, processes involving oxidative stress, inhibition of p21CIP1/WAF1

expression

and stimulation of N-terminal c-jun kinase and nuclear factor-kappaB. Therefore,

low-

dose diesel exhaust particle exposure may lead to lung epithelial cell

hyperplasia.