Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Respiratory Research
Published in: Respiratory Research 1/2005

Open Access 01-12-2005 | Research

Titanium dioxide particle – induced goblet cell hyperplasia : association with mast cells and IL-13

Authors: Mi-Hyun Ahn, Chun-Mi Kang, Choon-Sik Park, Sang-Jun Park, Taiyoun Rhim, Pyeong-Oh Yoon, Hun Soo Chang, Soo-Ho Kim, Hiroko Kyono, Kwang Chul Kim

Published in: Respiratory Research | Issue 1/2005

Login to get access

Abstract

Background

Inhalation of particles aggravates respiratory symptoms including mucus hypersecretion in patients with chronic airway disease and induces goblet cell hyperplasia (GCH) in experimental animal models. However, the underlying mechanisms remain poorly understood.

Methods

To understand this, the numbers of goblet cells, Muc5ac (+) expressing epithelial cells and IL-13 expressing mast cells were measured in the trachea of sham or TiO2 particles – treated rats using periodic acid-Schiff, toluidine blue and immunohistochemical staining. RT-PCR for Muc-1, 2 and 5ac gene transcripts was done using RNA extracted from the trachea. Differential cell count and IL-13 levels were measured in bronchoalveolar lavage (BAL) fluid. In pretreatment groups, cyclophosphamide (CPA) or dexamethasone (DEX) was given before instillation of TiO2. TiO2 treatment markedly increased Muc5ac mRNA expression, and Muc5ac (+) or PAS (+) epithelial cells 48 h following treatment.

Results

The concentration of IL-13 in BAL fluids was higher in TiO2 treated – rats when compared to those in sham rats (p < 0.05). Pretreatment with cyclophosphamide (CPA) decreased the number of neutrophils and eosinophils in BAL fluid of TiO2 treated – rats (p < 0.05), but affected neither the percentage of PAS (+) cells, nor IL-13 levels in the BAL fluids (p > 0.05). In contrast, pretreatment with dexamethasone (DEX) diminished the percentage of PAS (+) cells and the levels of IL-13 (p < 0.05). TiO2 treatment increased the IL-13 (+) mast cells (p < 0.05) in the trachea, which was suppressed by DEX (p < 0.05), but not by CPA pretreatment (p > 0.05). In addition there were significant correlations of IL-13 (+) rate of mast cells in the trachea with IL-13 concentration in BAL fluid (p < 0.01) and with the percentage of Muc5ac (+) cells in the sham and TiO2 treated rats (p < 0.05).

Conclusion

In conclusion, TiO2 instillation induces GCH and Muc5ac expression, and this process may be associated with increased production of IL-13 by mast cells.
Literature
1.
Openshaw PJ, Turner-Warwick M: Observations on sputum production in patients with variable airflow obstruction; Implications for the diagnosis of asthma and chronic bronchitis. Respir Med 1989, 83:25–31.CrossRefPubMed
2.
Thurlbeck WM, Malaka D, Murphy K: Goblet cells in the peripheral airways in chronic bronchitis. Am Rev Respir Dis 1975, 112:65–9.PubMed
3.
Aikawa T, Shimura S, Sasaki H, Ebina M, Takishima T: Marked goblet cell hyperplasia with mucus accumulation in the airways of patients who died of severe acute asthma attack. Chest 1992, 101:916–21.CrossRefPubMed
4.
Pope CA, Kanner RE: Acute effects of PM10 pollution on pulmonary function of smokers with mild to moderate chronic obstructive pulmonary disease. Am Rev Respir Dis 1993, 147:1336–40.CrossRefPubMed
5.
Schwartz J, Slater D, Larson TV, Pierson WE, Koenig JQ: Particulate air pollution and hospital emergency room visits for asthma in Seattle. Am Rev Respir Dis 1993, 147:826–31.CrossRefPubMed
6.
Pagan I, Costa DL, McGee JK, Richards JH, Dye JA: Metals mimic airway epithelial injury induced by in vitro exposure to Utah Valley ambient particulate matter extracts. J Toxicol Environ Health A 2003, 66:1087–112.CrossRefPubMed
7.
Seaton A, MacNee W, Donaldson K, Godden D: Particulate air pollution and acute health effects. Lancet 1995, 345:176–8.CrossRefPubMed
8.
Li XY, Gilmour PS, Donaldson K, MacNee W: Free radical activity and pro-inflammatory effects of particulate air pollution (PM 10 ) in vivo and in vitro. Thorax 1996, 51:1216–1222.CrossRefPubMedPubMedCentral
9.
Becker S, Soukup JM, Gilmour MI, Devlin RB: Stimulation of human and rat alveolar macrophages by urban air particulates: effects on oxidant radical generation and cytokine production. Toxicol Appl Pharmacol 1996, 141:637–48.CrossRefPubMed
10.
Fujii T, Hayashi S, Hogg JC, Vincent R, Van Eeden SF: Particulate matter induces cytokine expression in human bronchial epithelial cells. Am J Respir Cell Mol Biol 2001, 25:265–71.CrossRefPubMed
11.
Hamilton RF Jr, Holian A, Morandi MT: A comparison of asbestos and urban particulate matter in the in vitro modification of human alveolar macrophage antigen-presenting cell function. Exp Lung Res 2004, 30:147–62.CrossRefPubMed
12.
Li N, Hao M, Phalen RF, Hinds WC, Nel AE: Particulate air pollutants and asthma, A paradigm for the role of oxidative stress in PM-induced adverse health effects. Clinical Immunology 2003, 109:250–265.CrossRefPubMed
13.
Zhu Z, Homer RJ, Wang Z, Chen Q, Geba GP, Wang J, Whang Y, Elias JA: Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest 1999, 103:779–788.CrossRefPubMedPubMedCentral
14.
Grunig G, Warnock M, Wakil AE, Venkayya R, Brombacher F, Rennick DM, Sheppard D, Mohrs M, Donaldson DD, Locksley RM, Corry DB: Requirement for IL-13 independently of IL-4 in experimental asthma. Science 1998, 282:2261–3.CrossRefPubMedPubMedCentral
15.
Templeton DM: Titanium. In handbook on metals in clinical and analytic chemistry. Edited by: Seiler HG, Siegel A, Siegel H. New York: Marcel Dekker; 1994:627–30.
16.
Garabrant DH, Fine LJ, Oliver C, Bernstein L, Peters JM: Abnormalities of pulmonary function and pleural disease among titanium metal production workers. Scand J Work Environ Health 1987, 13:47–51.CrossRefPubMed
17.
Schapira RM, Ghio AJ, Effros RM, Morrisey J, Almagro UA, Dawson CA, Hacker AD: Hydroxyl radical production and lung injury in the rat following silica or titanium dioxide instillation in vivo. Am J Respir Cell Mol Biol 1995, 12:220–6.CrossRefPubMed
18.
Warheit DB, Hansen JF, Yuen IS, Kelly DP, Snajdr SI, Hartsky MA: Inhalation of high concentrations of low toxicity dusts in rats results in impaired pulmonary clearance mechanisms and persistent inflammation. Toxicol Appl Pharmacol 1997, 145:10–22.CrossRefPubMed
19.
Nagai H, Yamaguchi S, Tanaka H, Inagaki N: Effect of some immunosuppressors on allergic bronchial inflammation and airway hyperresponsiveness in mice. Int Arch Allergy Immunol 1995, 108:189–95.CrossRefPubMed
20.
Fushimi T, Okayama H, Shimura S, Saitoh H, Shirato K: Dexamethasone suppresses gene expression and production of IL-13 by human mast cell line and lung mast cells. J Allergy Clin Immunol 1998, 102:134–42.CrossRefPubMed
21.
Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987, 162:156–9.CrossRefPubMed
22.
Harkema JR, Hotchkiss JA: In vivo effects of endotoxin on intraepithelial mucosubstances in rat pulmonary airways. Quantitative histochemistry. Am J Pathol 1992, 141:307–17.PubMedPubMedCentral
23.
Cardozo C, Padilla ML, Choi HS, Lesser M: Goblet cell hyperplasia in large intrapulmonary airways after intratracheal injection of cathepsin B into hamsters. Am Rev Respir Dis 1992, 145:675–679.CrossRefPubMed
24.
Kibe A, Inoue H, Fukurama S, Machida K, Matsumoto K, Koto H, Ikegami T, Aizawa H, Hara N: Differential regulation by glucocorticoid of interleukin-13-induced eosinophilia, hyprresponsiveness, and goblet cell hyperplasia in mouse airways. Am J Respir Crit Care Med 2003, 167:50–56.CrossRefPubMed
25.
Dabbagh K, Takeyama K, Lee HM, Ueki IF, Lausier JA, Nadel JA: IL-4 induces mucin gene expression and goblet cell metaplasia in vitro and in vivo. J Immunol 1999, 162:6233–7.PubMed
26.
Ordonez CL, Khashayar R, Wong HH, Ferrando R, Wu R, Hyde DM, Hotchkiss JA, Zhang Y, Novikov A, Dolganov G, Fahy JV: Mild and moderate asthma is associated with airway goblet cell hyperplasia and abnormalities in mucin gene expression. Am J Respir Crit Care Med 2001, 163:517–523.CrossRefPubMed
27.
Lucey EC, Stone PJ, Breuer R, Christensen TG, Calore JD, Catanese A, Franzblau C, Snider GL: Effect of combined human neutrophil cathepsin G and elastase on induction of secretory cell metaplasia and emphysema in hamsters, with in vitro observations on elastolysis by these enzymes. Am Rev Respir Dis 1985, 132:362–6.PubMed
28.
Townsend MJ, Fallon PG, Matthews DJ, Smith P, Jolin HE, McKenzie ANJ: IL-9-deficient mice establish fundamental roles for IL-9 in pulmonary mastocytosis and goblet cell hyperplasia but not T cell development. Immunity 2000, 13:573–583.CrossRefPubMed
29.
Shim JJ, Dabbagh K, Ueki IF, Dao-Pick T, Burgel PR, Takeyama K, Tam DC, Nadel JA: IL-13 induces mucin production by stimulating epidermal growth factor receptors and by activating neutrophils. Am J Physiol Lung Cell Mol Physiol 2001, 280:L134–40.PubMed
30.
Singer M, Lefort J, Vargaftig BB: Granulocyte depletion and dexamethasone differentially modulate airways hyperreactivity, inflammation, mucus accumulation, and secretion induced by rmIL-13 or antigen. Am J Respir Cell Mol Biol 2002, 26:74–84.CrossRefPubMed
31.
Lee HM, Takeyama K, Dabbagh K, Lausier JA, Ueki IF, Nadel JA: Agarose plug instillation causes goblet cell metaplasia by activating EGF receptors in rat airways. Am J Physiol Lung Cell Mol Physiol 2000, 278:L185–92.PubMed
32.
Mathur M, Herrmann K, Li X, Qin Y, Weinstock J, Elliott D, Monahan J, Padrid P: TRFK-5 reverses established airway eosinophilia but not established hyperresponsiveness in a murine model of chronic asthma. Am J Respir Crit Care Med 1999, 159:580–7.CrossRefPubMed
33.
Cohn L, Homer RJ, MacLeod H, Mohrs M, Brombacher F, Bottomly K: Th2-induced airway mucus production is dependent on IL-4Ralpha, but not on eosinophils. J Immunol 1999, 162:6178–83.PubMed
34.
Whittaker L, Niu N, Temann UA, Stoddard A, Flavell RA, Ray A, Homer RJ, Cohn L: Interleukin-13 mediates a fundamental pathway for airway epithelial mucus induced by CD4 cells and interleukin-9. Am J Respir Cell Mol Biol 2002, 27:593–602.CrossRefPubMed
35.
Eum SY, Maghni K, Hamid Q, Eidelman DH, Campbell H, Isogai S, Martin JG: Inhibition of allergic airways inflammation and airway hyperresponsiveness in mice by dexamethasone : Role of eosinophils, IL-5, eotaxin, and IL-13. J Allergy Clin Immunol 2003, 111:1049–61.CrossRefPubMed
36.
Danahay H, Atherton H, Jones G, Bridges RJ, Poll CT: Interleukin-13 induces a hypersecretory ion transport phenotype in human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol 2002, 282:L226–36.CrossRefPubMed
37.
Zhou Y, Dong Q, Louahed J, Dragwa C, Savio D, Huang M, Weiss C, Tomer Y, McLane MP, Nicolaides NC, Levitt RC: Characterization of a calcium-activated chloride channel as a shared target of Th2 cytokine pathways and its potential involvement in asthma. Am J Respir Cell Mol Biol 2001, 25:486–91.CrossRefPubMed
38.
39.
Burd PR, Thompson WC, Max EE, Mills FC: Activated mast cells produce interleukin 13. J Exp Med 1995, 181:1373–80.CrossRefPubMed
40.
Hancock A, Lynne Armstrong , Rafael Gama , Ann Millar : Production of Interleukin 13 by alveolar macrophages from normal and fibrotic lung. Am J Respir Cell Mol Biol 1998, 18:60–65.CrossRefPubMed
Metadata
Title
Titanium dioxide particle – induced goblet cell hyperplasia : association with mast cells and IL-13
Authors
Mi-Hyun Ahn
Chun-Mi Kang
Choon-Sik Park
Sang-Jun Park
Taiyoun Rhim
Pyeong-Oh Yoon
Hun Soo Chang
Soo-Ho Kim
Hiroko Kyono
Kwang Chul Kim
Publication date
01-12-2005
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2005
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-6-34

Other articles of this Issue 1/2005

Respiratory Research 1/2005 Go to the issue

Research

Deficiency in type 1 insulin-like growth factor receptor in mice protects against oxygen-induced lung injury

Research

A role for MCP-1/CCR2 in interstitial lung disease in children

Research

Activation of the SPHK/S1P signalling pathway is coupled to muscarinic receptor-dependent regulation of peripheral airways

Research

Involvement of RhoA-mediated Ca2+ sensitization in antigen-induced bronchial smooth muscle hyperresponsiveness in mice

Research

A confocal microscopic study of solitary pulmonary neuroendocrine cells in human airway epithelium

Research

Mathematical modelling to centre low tidal volumes following acute lung injury: A study with biologically variable ventilation
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits