« Previous Next »The Journal of Allergy and Clinical Immunology
Volume 122, Issue 6 , Pages 1208-1214, December 2008

Cigarette smoke extract induces thymic stromal lymphopoietin expression, leading to TH2-type immune responses and airway inflammation

Yuki Nakamura
- Department of Immunology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
Masanori Miyata, MD
- Department of Immunology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
Tetsuro Ohba, MD
- Department of Immunology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
Takashi Ando, MD, PhD
- Department of Immunology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
Kyosuke Hatsushika, MD, PhD
- Department of Immunology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
Fumiko Suenaga
- Department of Immunology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
Naomi Shimokawa, PhD
- Department of Immunology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
Yuko Ohnuma
- Department of Immunology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
Ryohei Katoh, MD, PhD
- Department of Human Pathology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
Hideoki Ogawa, MD, PhD
- Atopy Research Center, Juntendo University School of Medicine, Tokyo, Japan
Atsuhito Nakao, MD, PhD
- Department of Immunology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
- Atopy Research Center, Juntendo University School of Medicine, Tokyo, Japan
- Reprint requests: Atsuhito Nakao, MD, PhD, Department of Immunology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan.

Received 7 February 2008; received in revised form 22 July 2008; accepted 15 September 2008. published online 17 October 2008.

Background

Both active and passive smoking are considered to be risk factors for asthma development. However, the precise mechanisms involved remain elusive. Recently, thymic stromal lymphopoietin (TSLP) has been shown to play a key role in the development of TH2-type allergic inflammation in patients with asthma.

Objective

The aim of this study was to investigate whether there was a causal relationship between cigarette smoke exposure and TSLP expression in the lung.

Methods

We examined the effects of repeated intranasal exposure of cigarette smoke extract (CSE) on TSLP mRNA and protein expression in the mouse lung by means of real-time PCR, Western blotting, and immunohistochemistry. We also examined the effects of intranasal exposure of CSE plus ovalbumin (OVA) on TH2-type immune responses and lung pathology.

Results

Repeated exposure of CSE induced TSLP mRNA and protein expression, which was inhibited by treatment with antioxidative N-acetylcysteine and by TNF-α receptor I deficiency. In addition, the intranasal exposure of CSE simultaneously with OVA induced OVA-specific TH2-type immune responses and airway inflammation, which were inhibited by the blockade of the TSLP activity.

Conclusion

CSE induced TSLP expression in the mouse lung in an oxidative stress–dependent and TNF-α receptor I–dependent manner, and when challenged simultaneously with an antigen, CSE promoted the development of airway inflammation in association with TH2-type immune responses.

Key words: Cigarette smoke, thymic stromal lymphopoietin, asthma, TH2

Abbreviations used: CSE, Cigarette smoke extract, mEAR2, Eosinophil-associated RNase2, NAC, N-acetylcysteine, OVA, Ovalbumin, TSLP, Thymic stromal lymphopoietin