Skip to main content
Top
Published in: Respiratory Research 1/2005

Open Access 01-12-2005 | Research

Up-regulation of Toll-like receptors 2, 3 and 4 in allergic rhinitis

Authors: Mattias Fransson, Mikael Adner, Jonas Erjefält, Lennart Jansson, Rolf Uddman, Lars-Olaf Cardell

Published in: Respiratory Research | Issue 1/2005

Login to get access

Abstract

Background

Toll-like receptors enable the host to recognize a large number of pathogen-associated molecular patterns such as bacterial lipopolysaccharide, viral RNA, CpG-containing DNA and flagellin. Toll-like receptors have also been shown to play a pivotal role in both innate and adaptive immune responses. The role of Toll-like receptors as a primary part of our microbe defense system has been shown in several studies, but their possible function as mediators in allergy and asthma remains to be established. The present study was designed to examine the expression of Toll-like receptors 2, 3 and 4 in the nasal mucosa of patients with intermittent allergic rhinitis, focusing on changes induced by exposure to pollen.

Methods

27 healthy controls and 42 patients with seasonal allergic rhinitis volunteered for the study. Nasal biopsies were obtained before and during pollen season as well as before and after allergen challenge. The seasonal material was used for mRNA quantification of Toll-like receptors 2, 3 and 4 with real-time polymerase chain reaction, whereas specimens achieved in conjunction with allergen challenge were used for immunohistochemical localization and quantification of corresponding proteins.

Results

mRNA and protein representing Toll-like receptors 2, 3 and 4 could be demonstrated in all specimens. An increase in protein expression for all three receptors could be seen following allergen challenge, whereas a significant increase of mRNA only could be obtained for Toll-like receptor 3 during pollen season.

Conclusion

The up-regulation of Toll-like receptors 2, 3 and 4 in the nasal mucosa of patients with symptomatic allergic rhinitis supports the idea of a role for Toll-like receptors in allergic airway inflammation.
Literature
1.
2.
go back to reference Vandermeer J, Sha Q, Lane AP, Schleimer RP: Innate immunity of the sinonasal cavity: expression of messenger RNA for complement cascade components and toll-like receptors. Arch Otolaryngol Head Neck Surg 2004, 130:1374–1380.CrossRefPubMed Vandermeer J, Sha Q, Lane AP, Schleimer RP: Innate immunity of the sinonasal cavity: expression of messenger RNA for complement cascade components and toll-like receptors. Arch Otolaryngol Head Neck Surg 2004, 130:1374–1380.CrossRefPubMed
3.
go back to reference Claeys S, de Belder T, Holtappels G, Gevaert P, Verhasselt B, van Cauwenberge P, Bachert C: Human beta-defensins and toll-like receptors in the upper airway. Allergy 2003, 58:748–753.CrossRefPubMed Claeys S, de Belder T, Holtappels G, Gevaert P, Verhasselt B, van Cauwenberge P, Bachert C: Human beta-defensins and toll-like receptors in the upper airway. Allergy 2003, 58:748–753.CrossRefPubMed
4.
go back to reference Sha Q, Truong-Tran AQ, Plitt JR, Beck LA, Schleimer RP: Activation of airway epithelial cells by toll-like receptor agonists. Am J Respir Cell Mol Biol 2004, 31:358–364.CrossRefPubMed Sha Q, Truong-Tran AQ, Plitt JR, Beck LA, Schleimer RP: Activation of airway epithelial cells by toll-like receptor agonists. Am J Respir Cell Mol Biol 2004, 31:358–364.CrossRefPubMed
5.
go back to reference Sabroe I, Read RC, Whyte MK, Dockrell DH, Vogel SN, Dower SK: Toll-like receptors in health and disease: complex questions remain. J Immunol 2003, 171:1630–1635.CrossRefPubMed Sabroe I, Read RC, Whyte MK, Dockrell DH, Vogel SN, Dower SK: Toll-like receptors in health and disease: complex questions remain. J Immunol 2003, 171:1630–1635.CrossRefPubMed
6.
go back to reference Zuany-Amorim C, Hastewell J, Walker C: Toll-like receptors as potential therapeutic targets for multiple diseases. Nat Rev Drug Discov 2002, 1:797–807.CrossRefPubMed Zuany-Amorim C, Hastewell J, Walker C: Toll-like receptors as potential therapeutic targets for multiple diseases. Nat Rev Drug Discov 2002, 1:797–807.CrossRefPubMed
7.
go back to reference O'Neill LA: Therapeutic targeting of Toll-like receptors for inflammatory and infectious diseases. Curr Opin Pharmacol 2003, 3:396–403.CrossRefPubMed O'Neill LA: Therapeutic targeting of Toll-like receptors for inflammatory and infectious diseases. Curr Opin Pharmacol 2003, 3:396–403.CrossRefPubMed
8.
go back to reference Heine H, Lien E: Toll-like receptors and their function in innate and adaptive immunity. Int Arch Allergy Immunol 2003, 130:180–192.CrossRefPubMed Heine H, Lien E: Toll-like receptors and their function in innate and adaptive immunity. Int Arch Allergy Immunol 2003, 130:180–192.CrossRefPubMed
9.
go back to reference Sabroe I, Parker LC, Wilson AG, Whyte MK, Dower SK: Toll-like receptors: their role in allergy and non-allergic inflammatory disease. Clin Exp Allergy 2002, 32:984–989.CrossRefPubMed Sabroe I, Parker LC, Wilson AG, Whyte MK, Dower SK: Toll-like receptors: their role in allergy and non-allergic inflammatory disease. Clin Exp Allergy 2002, 32:984–989.CrossRefPubMed
10.
go back to reference Cario E, Podolsky DK: Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect Immun 2000, 68:7010–7017.CrossRefPubMedPubMedCentral Cario E, Podolsky DK: Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect Immun 2000, 68:7010–7017.CrossRefPubMedPubMedCentral
11.
go back to reference Pitzurra L, Bellocchio S, Nocentini A, Bonifazi P, Scardazza R, Gallucci L, Stracci F, Simoncelli C, Bistoni F, Romani L: Antifungal immune reactivity in nasal polyposis. Infect Immun 2004, 72:7275–7281.CrossRefPubMedPubMedCentral Pitzurra L, Bellocchio S, Nocentini A, Bonifazi P, Scardazza R, Gallucci L, Stracci F, Simoncelli C, Bistoni F, Romani L: Antifungal immune reactivity in nasal polyposis. Infect Immun 2004, 72:7275–7281.CrossRefPubMedPubMedCentral
12.
go back to reference Muir A, Soong G, Sokol S, Reddy B, Gomez M, Van Heeckeren A, Prince A: Toll like receptors in normal and cystic fibrosis airway epithelial cells. Am J Respir Cell Mol Biol 2003, 4:4. Muir A, Soong G, Sokol S, Reddy B, Gomez M, Van Heeckeren A, Prince A: Toll like receptors in normal and cystic fibrosis airway epithelial cells. Am J Respir Cell Mol Biol 2003, 4:4.
13.
go back to reference Guillot L, Medjane S, Le-Barillec K, Balloy V, Danel C, Chignard M, Si-Tahar M: Response of human pulmonary epithelial cells to lipopolysaccharide involves Toll-like receptor 4 (TLR4)-dependent signaling pathways: evidence for an intracellular compartmentalization of TLR4. J Biol Chem 2004, 279:2712–2718.CrossRefPubMed Guillot L, Medjane S, Le-Barillec K, Balloy V, Danel C, Chignard M, Si-Tahar M: Response of human pulmonary epithelial cells to lipopolysaccharide involves Toll-like receptor 4 (TLR4)-dependent signaling pathways: evidence for an intracellular compartmentalization of TLR4. J Biol Chem 2004, 279:2712–2718.CrossRefPubMed
14.
go back to reference Monick MM, Yarovinsky TO, Powers LS, Butler NS, Carter AB, Gudmundsson G, Hunninghake GW: Respiratory syncytial virus up-regulates TLR4 and sensitizes airway epithelial cells to endotoxin. J Biol Chem 2003, 278:53035–53044.CrossRefPubMed Monick MM, Yarovinsky TO, Powers LS, Butler NS, Carter AB, Gudmundsson G, Hunninghake GW: Respiratory syncytial virus up-regulates TLR4 and sensitizes airway epithelial cells to endotoxin. J Biol Chem 2003, 278:53035–53044.CrossRefPubMed
15.
go back to reference Hertz CJ, Wu Q, Porter EM, Zhang YJ, Weismuller KH, Godowski PJ, Ganz T, Randell SH, Modlin RL: Activation of toll-like receptor 2 on human tracheobronchial epithelial cells induces the antimicrobial peptide human beta defensin-2. J Immunol 2003, 171:6820–6826.CrossRefPubMed Hertz CJ, Wu Q, Porter EM, Zhang YJ, Weismuller KH, Godowski PJ, Ganz T, Randell SH, Modlin RL: Activation of toll-like receptor 2 on human tracheobronchial epithelial cells induces the antimicrobial peptide human beta defensin-2. J Immunol 2003, 171:6820–6826.CrossRefPubMed
16.
go back to reference Armstrong L, Medford AR, Uppington KM, Robertson J, Witherden IR, Tetley TD, Millar AB: Expression of functional toll-like receptor-2 and -4 on alveolar epithelial cells. Am J Respir Cell Mol Biol 2004, 31:241–245.CrossRefPubMed Armstrong L, Medford AR, Uppington KM, Robertson J, Witherden IR, Tetley TD, Millar AB: Expression of functional toll-like receptor-2 and -4 on alveolar epithelial cells. Am J Respir Cell Mol Biol 2004, 31:241–245.CrossRefPubMed
17.
go back to reference Tulic MK, Fiset PO, Manoukian JJ, Frenkiel S, Lavigne F, Eidelman DH, Hamid Q: Role of toll-like receptor 4 in protection by bacterial lipopolysaccharide in the nasal mucosa of atopic children but not adults. Lancet 2004, 363:1689–1697.CrossRefPubMed Tulic MK, Fiset PO, Manoukian JJ, Frenkiel S, Lavigne F, Eidelman DH, Hamid Q: Role of toll-like receptor 4 in protection by bacterial lipopolysaccharide in the nasal mucosa of atopic children but not adults. Lancet 2004, 363:1689–1697.CrossRefPubMed
18.
go back to reference Aas K, Belin L: Standardization of diagnostic work in allergy. Int Arch Allergy Appl Immunol 1973, 45:57–60.CrossRefPubMed Aas K, Belin L: Standardization of diagnostic work in allergy. Int Arch Allergy Appl Immunol 1973, 45:57–60.CrossRefPubMed
19.
go back to reference Muzio M, Bosisio D, Polentarutti N, D'Amico G, Stoppacciaro A, Mancinelli R, van't Veer C, Penton-Rol G, Ruco LP, Allavena P, et al.: Differential expression and regulation of toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells. J Immunol 2000, 164:5998–6004.CrossRefPubMed Muzio M, Bosisio D, Polentarutti N, D'Amico G, Stoppacciaro A, Mancinelli R, van't Veer C, Penton-Rol G, Ruco LP, Allavena P, et al.: Differential expression and regulation of toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells. J Immunol 2000, 164:5998–6004.CrossRefPubMed
20.
go back to reference Kaisho T, Akira S: Regulation of dendritic cell function through Toll-like receptors. Curr Mol Med 2003, 3:373–385.CrossRefPubMed Kaisho T, Akira S: Regulation of dendritic cell function through Toll-like receptors. Curr Mol Med 2003, 3:373–385.CrossRefPubMed
21.
22.
go back to reference Soong G, Reddy B, Sokol S, Adamo R, Prince A: TLR2 is mobilized into an apical lipid raft receptor complex to signal infection in airway epithelial cells. J Clin Invest 2004, 113:1482–1489.CrossRefPubMedPubMedCentral Soong G, Reddy B, Sokol S, Adamo R, Prince A: TLR2 is mobilized into an apical lipid raft receptor complex to signal infection in airway epithelial cells. J Clin Invest 2004, 113:1482–1489.CrossRefPubMedPubMedCentral
23.
go back to reference Greene CM, Carroll TP, Smith SG, Taggart CC, Devaney J, Griffin S, O'Neill SJ, McElvaney NG: TLR-induced inflammation in cystic fibrosis and non-cystic fibrosis airway epithelial cells. J Immunol 2005, 174:1638–1646.CrossRefPubMed Greene CM, Carroll TP, Smith SG, Taggart CC, Devaney J, Griffin S, O'Neill SJ, McElvaney NG: TLR-induced inflammation in cystic fibrosis and non-cystic fibrosis airway epithelial cells. J Immunol 2005, 174:1638–1646.CrossRefPubMed
24.
go back to reference Matsumoto M, Funami K, Tanabe M, Oshiumi H, Shingai M, Seto Y, Yamamoto A, Seya T: Subcellular localization of Toll-like receptor 3 in human dendritic cells. J Immunol 2003, 171:3154–3162.CrossRefPubMed Matsumoto M, Funami K, Tanabe M, Oshiumi H, Shingai M, Seto Y, Yamamoto A, Seya T: Subcellular localization of Toll-like receptor 3 in human dendritic cells. J Immunol 2003, 171:3154–3162.CrossRefPubMed
25.
go back to reference Matsumoto M, Kikkawa S, Kohase M, Miyake K, Seya T: Establishment of a monoclonal antibody against human Toll-like receptor 3 that blocks double-stranded RNA-mediated signaling. Biochem Biophys Res Commun 2002, 293:1364–1369.CrossRefPubMed Matsumoto M, Kikkawa S, Kohase M, Miyake K, Seya T: Establishment of a monoclonal antibody against human Toll-like receptor 3 that blocks double-stranded RNA-mediated signaling. Biochem Biophys Res Commun 2002, 293:1364–1369.CrossRefPubMed
26.
go back to reference Shuto T, Imasato A, Jono H, Sakai A, Xu H, Watanabe T, Rixter DD, Kai H, Andalibi A, Linthicum F, et al.: Glucocorticoids synergistically enhance nontypeable Haemophilus influenzae-induced Toll-like receptor 2 expression via a negative cross-talk with p38 MAP kinase. J Biol Chem 2002, 277:17263–17270.CrossRefPubMed Shuto T, Imasato A, Jono H, Sakai A, Xu H, Watanabe T, Rixter DD, Kai H, Andalibi A, Linthicum F, et al.: Glucocorticoids synergistically enhance nontypeable Haemophilus influenzae-induced Toll-like receptor 2 expression via a negative cross-talk with p38 MAP kinase. J Biol Chem 2002, 277:17263–17270.CrossRefPubMed
29.
go back to reference Lauener RP, Birchler T, Adamski J, Braun-Fahrlander C, Bufe A, Herz U, von Mutius E, Nowak D, Riedler J, Waser M, et al.: Expression of CD14 and Toll-like receptor 2 in farmers' and non-farmers' children. Lancet 2002, 360:465–466.CrossRefPubMed Lauener RP, Birchler T, Adamski J, Braun-Fahrlander C, Bufe A, Herz U, von Mutius E, Nowak D, Riedler J, Waser M, et al.: Expression of CD14 and Toll-like receptor 2 in farmers' and non-farmers' children. Lancet 2002, 360:465–466.CrossRefPubMed
30.
go back to reference Use of antibiotics to treat asthma exacerbationsJ Allergy Clin Immunol 2002, 110:S180–183. Use of antibiotics to treat asthma exacerbationsJ Allergy Clin Immunol 2002, 110:S180–183.
31.
go back to reference Skoner DP: Viral infection and allergy: lower airway. Allergy Asthma Proc 2002, 23:229–232.PubMed Skoner DP: Viral infection and allergy: lower airway. Allergy Asthma Proc 2002, 23:229–232.PubMed
33.
go back to reference Blease K, Kunkel SL, Hogaboam CM: IL-18 modulates chronic fungal asthma in a murine model; putative involvement of Toll-like receptor-2. Inflamm Res 2001, 50:552–560.CrossRefPubMed Blease K, Kunkel SL, Hogaboam CM: IL-18 modulates chronic fungal asthma in a murine model; putative involvement of Toll-like receptor-2. Inflamm Res 2001, 50:552–560.CrossRefPubMed
Metadata
Title
Up-regulation of Toll-like receptors 2, 3 and 4 in allergic rhinitis
Authors
Mattias Fransson
Mikael Adner
Jonas Erjefält
Lennart Jansson
Rolf Uddman
Lars-Olaf Cardell
Publication date
01-12-2005
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2005
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-6-100

Other articles of this Issue 1/2005

Respiratory Research 1/2005 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

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.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

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

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

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

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