Toll-like receptors 2, 3 and 4 and thymic stromal lymphopoietin expression in fatal asthma
Carregando...
Citações na Scopus
49
Tipo de produção
article
Data de publicação
2012
Título da Revista
ISSN da Revista
Título do Volume
Editora
WILEY-BLACKWELL
Autores
MEDEIROS, M. C. R.
YICK, C. Y.
STERK, P. J.
SAMPAIO, J. L. M.
Citação
CLINICAL AND EXPERIMENTAL ALLERGY, v.42, n.10, p.1459-1471, 2012
Resumo
Background Airway inflammation in asthma involves innate immune responses. Toll-like receptors (TLRs) and thymic stromal lymphopoietin (TSLP) are thought to be involved in airway inflammation, but their expression in asthmatics both large and small airways has not been investigated. Objective To analyse the expression of TLR2, TLR3, TLR4 and TSLP in large and small airways of asthmatics and compare their expression in smoking and non-smoking asthmatics; to investigate whether TLR expression is associated with eosinophilic or neutrophilic airway inflammation and with Mycoplasma pneumoniae and Chlamydophila pneumoniae infection. Methods Using immunohistochemistry and image analysis, we investigated TLR2, TLR3, TLR4 and TSLP expression in large and small airways of 24 victims of fatal asthma, FA, (13 non-smokers, 11 smokers) and nine deceased control subjects (DCtrl). TLRs were also measured in 18 mild asthmatics (MA) and 12 healthy controls (HCtrl). M. pneumoniae and C. pneumoniae in autopsy lung tissue were analysed using real-time polymerase chain reaction. Airway eosinophils and neutrophils were measured in all subjects. Results Fatal asthma patients had higher TLR2 in the epithelial and outer layers of large and small airways compared with DCtrls. Smoking asthmatics had lower TLR2 levels in the inner and outer layers of the small airways than non-smoking asthmatics. TSLP was increased in the epithelial and outer layers of the large airways of FA. FA patients had greater TLR3 expression in the outer layer of large airways and greater TLR4 expression in the outer layer of small airways. Eosinophilic airway inflammation was associated with TLR expression in the epithelium of FA. No bacterial DNA was detected in FA or DCtrls. MA and HCtrls had only a small difference in TLR3 expression. Conclusions and Clinical Relevance Increased expression of TLR 2, 3 and 4 and TSLP in fatal asthma may contribute to the acute inflammation surrounding asthma deaths.
Palavras-chave
immunohistochemistry, innate immunity, lung
Referências
- Agrawal S, 2003, J IMMUNOL, V171, P4984
- Akdis CA, 2003, EUR J IMMUNOL, V33, P2717, DOI 10.1002/eji.200323329
- Allakhverdi Z, 2007, J EXP MED, V204, P253, DOI 10.1084/jem.20062211
- Araujo BB, 2008, EUR RESPIR J, V32, P61, DOI 10.1183/09031936.00147807
- Busse WW, 2001, NEW ENGL J MED, V344, P350
- Chu HW, 2005, J IMMUNOL, V174, P5713
- Cohn L, 2004, ANNU REV IMMUNOL, V22, P789, DOI 10.1146/annurev.immunol.22.012703.104716
- da Costa CUP, 2004, EUR J IMMUNOL, V34, P2874, DOI 10.1002/eji.200425101
- de Mello GCF, 2010, RESPIRATION, V79, P322, DOI 10.1159/000235722
- Dolhnikoff M, 2009, J ALLERGY CLIN IMMUN, V123, P1090, DOI 10.1016/j.jaci.2009.02.032
- Droemann D, 2005, RESP RES, V6, DOI 10.1186/1465-9921-6-68
- Eder W, 2004, J ALLERGY CLIN IMMUN, V113, P482, DOI 10.1016/j.jaci.2003.12.374
- Ferreira DS, 2008, EUR RESPIR J, V32, P2978
- Ferreira DS, 2007, AM J RESP CRIT CARE, V175, pA687
- Ferreira DS, 2009, WORLD ALL C, P389
- Ferreira DS, 2009, EUR RESPIR J, V34, P1610
- Fregonese L, 2005, J ALLERGY CLIN IMMUN, V115, P1148, DOI 10.1016/j.jaci.2005.01.068
- Green RM, 2002, BRIT MED J, V324, P763, DOI 10.1136/bmj.324.7340.763
- GROULS V, 1981, STAIN TECHNOL, V56, P323
- Hewson CA, 2005, J VIROL, V79, P12273, DOI 10.1128/JVI.79.19.12273-12279.2005
- Hilty M, 2010, PLOS ONE, V5, DOI 10.1371/journal.pone.0008578
- Huang YJ, 2011, J ALLERGY CLIN IMMUN, V127, P372, DOI 10.1016/j.jaci.2010.10.048
- Johnston SL, 2005, AM J RESP CRIT CARE, V172, P1078, DOI 10.1164/rccm.200412-1743PP
- Kelly MM, 2010, J ALLERGY CLIN IMMUN, V125, P349, DOI 10.1016/j.jaci.2009.09.011
- Macek V, 1999, Can Respir J, V6, P37
- Martin RJ, 2001, J ALLERGY CLIN IMMUN, V107, P595
- Mauad T, 2004, AM J RESP CRIT CARE, V170, P857, DOI 10.1164/rccm.200403-305OC
- MICHEL O, 1989, J APPL PHYSIOL, V66, P1059
- Michel O, 1996, AM J RESP CRIT CARE, V154, P1641
- Miyashita N, 1998, ANN ALLERG ASTHMA IM, V80, P405
- Netea MG, 2002, EUR J IMMUNOL, V32, P1188, DOI 10.1002/1521-4141(200204)32:4<1188::AID-IMMU1188>3.3.CO;2-1
- NICHOLSON KG, 1993, BRIT MED J, V307, P982
- O'Sullivan S, 2001, AM J RESP CRIT CARE, V164, P560
- Re F, 2001, J BIOL CHEM, V276, P37692, DOI 10.1074/jbc.M105927200
- Redecke V, 2004, J IMMUNOL, V172, P2739
- Shiang C, 2009, CLIN EXP ALLERGY, V39, P1499, DOI 10.1111/j.1365-2222.2009.03281.x
- Shikotra A, 2012, J ALLERGY CLIN IMMUN, V129, P104, DOI 10.1016/j.jaci.2011.08.031
- Simoes SD, 2005, CLIN EXP ALLERGY, V35, P602, DOI 10.1111/j.1365-2222.2005.02235.x
- Simpson JL, 2007, THORAX, V62, P211, DOI 10.1136/thx.2006.061358
- Soumelis V, 2002, NAT IMMUNOL, V3, P673, DOI 10.1038/ni805
- Sukkar MB, 2006, J ALLERGY CLIN IMMUN, V118, P641, DOI 10.1016/j.jaci.2006.05.013
- Takeda K, 2003, ANNU REV IMMUNOL, V21, P335, DOI 10.1146/annurev.immunol.21.120601.141126
- Talbot TR, 2005, NEW ENGL J MED, V352, P2082, DOI 10.1056/NEJMoa044113
- Taylor RC, 2006, J ALLERGY CLIN IMMUN, V117, P1148, DOI 10.1016/j.jaci.2006.02.014
- Thomson NC, 2004, EUR RESPIR J, V24, P822, DOI 10.1183/09031936.04.00039004
- Tsoumakidou M, 2007, AM J RESP CRIT CARE, V175, P919, DOI 10.1164/rccm.200607-908OC
- Vercammen E, 2008, CLIN MICROBIOL REV, V21, P13, DOI 10.1128/CMR.00022-07
- Wark PAB, 2005, J EXP MED, V201, P937, DOI 10.1084/jem.20041901
- Watson MW, 2003, RESPIROLOGY, V8, P234, DOI 10.1046/j.1440-1843.2003.00462.x
- Jeffery P, 2003, AM J RESP CRIT CARE, V168, pS1, DOI 10.1164/rccm.200202-150WS
- Wood LG, 2011, CLIN EXP ALLERGY, V41, P640, DOI 10.1111/j.1365-2222.2010.03669.x
- Yick CY, 2012, ALLERGY, V67, P552, DOI 10.1111/j.1398-9995.2011.02773.x
- Ying S, 2005, J IMMUNOL, V174, P8183
- Ying S, 2008, J IMMUNOL, V181, P2790
- [Anonymous], GLOB STRAT ASTHM MAN