Volume 40, Issue 5 pp. 763-771

Transforming growth factor-β stimulates the expression of eotaxin/CC chemokine ligand 11 and its promoter activity through binding site for nuclear factor-κB in airway smooth muscle cells

S. Matsukura,

S. Matsukura

First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan

Search for more papers by this author

M. Odaka,

M. Odaka

First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan

Search for more papers by this author

M. Kurokawa,

M. Kurokawa

First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan

Search for more papers by this author

H. Kuga,

H. Kuga

First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan

Search for more papers by this author

T. Homma,

T. Homma

First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan

Search for more papers by this author

H. Takeuchi,

H. Takeuchi

First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan

Search for more papers by this author

K. Notomi,

K. Notomi

First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan

Search for more papers by this author

F. Kokubu,

F. Kokubu

Department of Respiratory Internal Medicine, Showa University Fujigaoka Hospital, Kanagawa, Japan

Search for more papers by this author

M. Kawaguchi,

M. Kawaguchi

Department of Respiratory Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan

Search for more papers by this author

R. P. Schleimer,

R. P. Schleimer

Allergy-Immunology Division, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

Search for more papers by this author

M. W. Johnson,

M. W. Johnson

GlaxoSmithKline R&D, Respiratory Science, Greenford, Middlesex, UK

Search for more papers by this author

M. Adachi,

M. Adachi

First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan

Search for more papers by this author

S. Matsukura,

S. Matsukura

First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan

Search for more papers by this author

M. Odaka,

M. Odaka

First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan

Search for more papers by this author

M. Kurokawa,

M. Kurokawa

First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan

Search for more papers by this author

H. Kuga,

H. Kuga

First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan

Search for more papers by this author

T. Homma,

T. Homma

First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan

Search for more papers by this author

H. Takeuchi,

H. Takeuchi

First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan

Search for more papers by this author

K. Notomi,

K. Notomi

First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan

Search for more papers by this author

F. Kokubu,

F. Kokubu

Department of Respiratory Internal Medicine, Showa University Fujigaoka Hospital, Kanagawa, Japan

Search for more papers by this author

M. Kawaguchi,

M. Kawaguchi

Department of Respiratory Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan

Search for more papers by this author

R. P. Schleimer,

R. P. Schleimer

Allergy-Immunology Division, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

Search for more papers by this author

M. W. Johnson,

M. W. Johnson

GlaxoSmithKline R&D, Respiratory Science, Greenford, Middlesex, UK

Search for more papers by this author

M. Adachi,

M. Adachi

First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan

Search for more papers by this author

First published: 19 April 2010

https://doi.org/10.1111/j.1365-2222.2010.03474.x

Citations: 17

Correspondence:
Satoshi Matsukura, First Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
E-mail: [email protected]

Share a link

Email
Wechat
Bluesky

Summary

Background Chemokines ligands of CCR3 including eotaxin/CC chemokine ligand 11 (CCL11) may contribute to the pathogenesis of asthma. These chemokines and a growth factor (TGF-β) may be involved in the process of airway remodelling.

Objective We analysed the effects of TGF-β on the expression of CCR3 ligands in human airway smooth muscle (HASM) cells and investigated the mechanisms.

Methods HASM cells were cultured and treated with TGF-β and Th2 cytokines IL-4 or IL-13. Expression of mRNA was analysed by real-time PCR. Secretion of CCL11 into the culture medium was analysed by ELISA. Transcriptional regulation of CCL11 was analysed by luciferase assay using CCL11 promoter–luciferase reporter plasmids.

Results IL-4 or IL-13 significantly up-regulated the expression of mRNAs for CCL11 and CCL26. TGF-β alone did not increase the expression of chemokine mRNAs, but enhanced the induction of only CCL11 by IL-4 or IL-13 among CCR3 ligands. Activity of the CCL11 promoter was stimulated by IL-4, and this activity was enhanced by TGF-β. Activation by IL-4 or IL-4 plus TGF-β was lost by mutation of the binding site for signal transducers and activators of transcription-6 (STAT6) in the promoter. Cooperative activation by IL-4 and TGF-β was inhibited by mutation of the binding site for nuclear factor-κB (NF-κB) in the promoter. Pretreatment with an inhibitor of NF-κB and glucocorticoid fluticasone propionate significantly inhibited the expression of CCL11 mRNA induced by IL-4 plus TGF-β, indicating the importance of NF-κB in the cooperative activation of CCL11 transcription by TGF-β and IL-4.

Conclusion These results indicate that Th2 cytokines and TGF-β may contribute to the pathogenesis of asthma by stimulating expression of CCL11. The transcription factors STAT6 and NF-κB may play pivotal roles in this process.

Cite this as: S. Matsukura, M. Odaka, M. Kurokawa, H. Kuga, T. Homma, H. Takeuchi, K. Notomi, F. Kokubu, M. Kawaguchi, R. P. Schleimer, M. W. Johnson and M. Adachi, Clinical & Experimental Allergy, 2010 (40) 763–771.

References

1 Elias J, Lee C, Zheng T, Ma B, Homer R, Zhu Z. New insights into the pathogenesis of asthma. J Clin Invest 2003; 111: 291–7.
10.1172/JCI17748
CAS PubMed Web of Science® Google Scholar
2 Panettieri R. Jr Asthma persistence versus progression: does airway smooth muscle function predict irreversible airflow obstruction? Allergy Asthma Proc 2009; 30: 103–8.
Web of Science® Google Scholar
3 Bergeron C, Al-Ramli W, Hamid Q. Remodeling in asthma. Proc Am Thorac Soc 2009; 6: 301–5.
10.1513/pats.200808-089RM
PubMed Google Scholar
4 Black J, Roth M. Intrinsic asthma: is it intrinsic to the smooth muscle? Clin Exp Allergy 2009; 39: 962–5.
CAS PubMed Web of Science® Google Scholar
5 Ghaffar O, Hamid Q, Renzi P et al. Constitutive and cytokine-stimulated expression of eotaxin by human airway smooth muscle cells. Am J Respir Crit Care Med 1999; 159: 1933–42.
10.1164/ajrccm.159.6.9805039
CAS PubMed Web of Science® Google Scholar
6 Jose PJ, Griffiths-Johnson DA, Collins PD et al. Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflamations. J Exp Med 1994; 179: 881–7.
Google Scholar
7 Stellato C, Collins P, Ponath P et al. Production of the novel C-C chemokine MCP-4 by airway cells and comparison of its biological activity to other C-C chemokines. J Clin Invest 1997; 99: 926–36.
10.1172/JCI119257
CAS PubMed Web of Science® Google Scholar
8 Ying S, Meng Q, Zeibecoglou K et al. Eosinophil chemotactic chemokines (eotaxin, eotaxin-2, RANTES, monocyte chemoattractant protein-3 (MCP-3), and MCP-4), and C-C chemokine receptor 3 expression in bronchial biopsies from atopic and nonatopic (intrinsic) asthmatics. J Immunol 1999; 163: 6321–9.
10.4049/jimmunol.163.11.6321
CAS PubMed Web of Science® Google Scholar
9 Brightling C, Bradding P, Symon F, Holgate S, Wardlaw A, Pavord I. Mast-cell infiltration of airway smooth muscle in asthma. N Engl J Med 2002; 346: 1699–705.
10.1056/NEJMoa012705
PubMed Web of Science® Google Scholar
10 Ochi H, Hirani W, Yuan Q, Friend D, Austen K, Boyce J. T helper cell type 2 cytokine-mediated comitogenic responses and CCR3 expression during differentiation of human mast cells in vitro. J Exp Med 1999; 190: 267–80.
10.1084/jem.190.2.267
CAS PubMed Web of Science® Google Scholar
11 Odaka M, Matsukura S, Kuga H et al. Differential regulation of chemokine expression by Th1 and Th2 cytokines and mechanisms of eotaxin/CCL-11 expression in human airway smooth muscle cells. Int Arch Allergy Immunol 2007; 143 (Suppl. 1): 84–8.
10.1159/000101412
CAS PubMed Web of Science® Google Scholar
12 Matsukura S, Kokubu F, Kurokawa M et al. Molecular mechanisms of repression of eotaxin expression with fluticasone propionate in airway epithelial cells. Int Arch Allergy Immunol 2004; 134: S12–20.
10.1159/000077787
CAS Web of Science® Google Scholar
13 Matsukura S, Stellato C, Plitt J et al. Activation of eotaxin gene transcription by NF-kappa B and STAT6 in human airway epithelial cells. J Immunol 1999; 163: 6876–83.
10.4049/jimmunol.163.12.6876
CAS PubMed Web of Science® Google Scholar
14 Wenzel S, Trudeau J, Barnes S et al. TGF-beta and IL-13 synergistically increase eotaxin-1 production in human airway fibroblasts. J Immunol 2002; 169: 4613–9.
10.4049/jimmunol.169.8.4613
CAS PubMed Web of Science® Google Scholar
15 Zuyderduyn S, Hiemstra P, Rabe K. TGF-beta differentially regulates TH2 cytokine-induced eotaxin and eotaxin-3 release by human airway smooth muscle cells. J Allergy Clin Immunol 2004; 114: 791–8.
10.1016/j.jaci.2004.06.037
CAS PubMed Web of Science® Google Scholar
16 Krymskaya V, Hoffman R, Eszterhas A, Ciocca V, Panettieri R. TGF-beta 1 modulates EGF-stimulated phosphatidylinositol 3-kinase activity in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 1997; 273 (Part 1): L1220–7.
CAS PubMed Google Scholar
17 Hirst S, Hallsworth M, Peng Q, Lee T. Selective induction of eotaxin release by interleukin-13 or interleukin-4 in human airway smooth muscle cells is synergistic with interleukin-1beta and is mediated by the interleukin-4 receptor alpha-chain. Am J Respir Crit Care Med 2002; 165: 1161–71.
10.1164/ajrccm.165.8.2107158
PubMed Web of Science® Google Scholar
18 Peng Q, Matsuda T, Hirst S. Signaling pathways regulating interleukin-13-stimulated chemokine release from airway smooth muscle. Am J Respir Crit Care Med 2004; 169: 596–603.
10.1164/rccm.200307-888OC
PubMed Web of Science® Google Scholar
19 Rahimi R, Leof E. TGF-beta signaling: a tale of two responses. J Cell Biochem 2007; 102: 593–608.
CAS PubMed Web of Science® Google Scholar
20 Zawel L, Dai J, Buckhaults P et al. Human Smad3 and Smad4 are sequence-specific transcription activators. Mol Cell 1998; 1: 611–7.
10.1016/S1097-2765(00)80061-1
CAS PubMed Web of Science® Google Scholar
21 Dennler S, Itoh S, Vivien D, Dijke P, Huet S, Gauthier J. Direct binding of Smad3 and Smad4 to critical TGF beta-inducible elements in the promoter of human plasminogen activator inhibitor-type 1 gene. EMBO J 1998; 17: 3091–100.
10.1093/emboj/17.11.3091
CAS PubMed Web of Science® Google Scholar
22 Hein H, Schluter C, Kulke R, Christophers E, Schroder J, Bartels J. Genomic organization, sequence, and transcriptional regulation of the human eotaxin gene. Biochem Biophys Res Commun 1997; 237: 537–42.
10.1006/bbrc.1997.7169
CAS PubMed Web of Science® Google Scholar
23 Garcia-Zepeda E, Rothenberg M, Weremowicz S, Sarafi M, Morton C, Luster A. Genomic organization, complete sequence, and chromosomal location of the gene for human eotaxin (SCYA11), an eosinophil-specific CC chemokine. Genomics 1997; 41: 471–6.
10.1006/geno.1997.4656
CAS PubMed Web of Science® Google Scholar
24 Scheinman R, Gualberto A, Jewell C, Cidlowski J, Baldwin A. Characterization of mechanisms involved in transrepression of NF-kappa B by activated glucocorticoid receptors. Mol Cell Biol 1995; 15: 943–53.
10.1128/MCB.15.2.943
CAS PubMed Web of Science® Google Scholar
25 Stellato C, Matsukura S, Fal A et al. Differential regulation of epithelial-derived C-C chemokine expression by IL-4 and the glucocorticoid budesonide. J Immunol 1999; 163: 5624–32.
CAS PubMed Web of Science® Google Scholar
26 Joubert P, Lajoie-Kadoch S, Labonte I et al. CCR3 expression and function in asthmatic airway smooth muscle cells. J Immunol 2005; 175: 2702–8.
10.4049/jimmunol.175.4.2702
CAS PubMed Web of Science® Google Scholar
27 Pang L, Knox A. Synergistic inhibition by beta(2)-agonists and corticosteroids on tumor necrosis factor-alpha-induced interleukin-8 release from cultured human airway smooth-muscle cells. Am J Respir Cell Mol Biol 2000; 23: 79–85.
10.1165/ajrcmb.23.1.3985
CAS PubMed Web of Science® Google Scholar
28 Ammit A, Lazaar A, Irani C et al. Tumor necrosis factor-alpha-induced secretion of RANTES and interleukin-6 from human airway smooth muscle cells: modulation by glucocorticoids and beta-agonists. Am J Respir Cell Mol Biol 2002; 26: 465–74.
CAS PubMed Web of Science® Google Scholar
29 Pang L, Knox A. Regulation of TNF-alpha-induced eotaxin release from cultured human airway smooth muscle cells by beta2-agonists and corticosteroids. FASEB J 2001; 15: 261–9.
10.1096/fj.00-0103com
CAS PubMed Web of Science® Google Scholar
30 Nie M, Knox A, Pang L. beta2-Adrenoceptor agonists, like glucocorticoids, repress eotaxin gene transcription by selective inhibition of histone H4 acetylation. J Immunol 2005; 175: 478–86.
10.4049/jimmunol.175.1.478
CAS PubMed Web of Science® Google Scholar
31 Hein H, Schlüter C, Kulke R, Christophers E, Schröder J, Bartels J. Genomic organization, sequence analysis and transcriptional regulation of the human MCP-4 chemokine gene (SCYA13) in dermal fibroblasts: a comparison to other eosinophilic beta-chemokines. Biochem Biophys Res Commun 1999; 255: 470–6.
CAS PubMed Web of Science® Google Scholar
32 Kalayci O, Birben E, Wu L et al. Monocyte chemoattractant protein-4 core promoter genetic variants: influence on YY-1 affinity and plasma levels. Am J Respir Cell Mol Biol 2003; 29: 750–6.
CAS PubMed Web of Science® Google Scholar
33 Kurisaki K, Kurisaki A, Valcourt U et al. Nuclear factor YY1 inhibits transforming growth factor beta- and bone morphogenetic protein-induced cell differentiation. Mol Cell Biol 2003; 23: 4494–510.
10.1128/MCB.23.13.4494-4510.2003
CAS PubMed Web of Science® Google Scholar
34 Ying S, Robinson DS, Meng Q et al. Enhanced expression of eotaxin and CCR3 mRNA and protein in atopic asthma. Association with airway hyperresponsiveness and predominant co-localization of eotaxin mRNA to bronchial epithelial and endothelial cells. Eur J Immunol 1997; 27: 3507–16.
10.1002/eji.1830271252
CAS PubMed Web of Science® Google Scholar
35 Vignola A, Chanez P, Chiappara G et al. Transforming growth factor-beta expression in mucosal biopsies in asthma and chronic bronchitis. Am J Respir Crit Care Med 1997; 156: 591–9.
10.1164/ajrccm.156.2.9609066
CAS PubMed Web of Science® Google Scholar
36 Minshall E, Leung D, Martin R et al. Eosinophil-associated TGF-beta1 mRNA expression and airways fibrosis in bronchial asthma. Am J Respir Cell Mol Biol 1997; 17: 326–33.
10.1165/ajrcmb.17.3.2733
CAS PubMed Web of Science® Google Scholar

Citing Literature

Volume40, Issue5

May 2010

Pages 763-771

Transforming growth factor-β stimulates the expression of eotaxin/CC chemokine ligand 11 and its promoter activity through binding site for nuclear factor-κB in airway smooth muscle cells

Summary

References

Citing Literature

References

Information

About Wiley Online Library

Help & Support

Opportunities

Connect with Wiley

Transforming growth factor-β stimulates the expression of eotaxin/CC chemokine ligand 11 and its promoter activity through binding site for nuclear factor-κB in airway smooth muscle cells

Summary

References

Citing Literature

References

Related

Information