Th17/Treg imbalance in COPD progression: A temporal analysis using a CS-induced model
Carregando...
Citações na Scopus
36
Tipo de produção
article
Data de publicação
2019
Título da Revista
ISSN da Revista
Título do Volume
Editora
PUBLIC LIBRARY SCIENCE
Citação
PLOS ONE, v.14, n.1, article ID e0209351, 19p, 2019
Resumo
Background The imbalance between pro- and anti-inflammatory immune responses plays a pivotal role in chronic obstructive pulmonary disease (COPD) development and progression. To clarify the pathophysiological mechanisms of this disease, we performed a temporal analysis of immune response-mediated inflammatory progression in a cigarette smoke (CS)-induced mouse model with a focus on the balance between Th17 and Treg responses. Methods C57BL/6 mice were exposed to CS for 1, 3 or 6 months to induce COPD, and the control groups were maintained under filtered air conditions for the same time intervals. We then performed functional (respiratory mechanics) and structural (alveolar enlargement) analyses. We also quantified the NF-kappa B, TNF-alpha, CD4, CD8, CD20, IL-17, IL-6, FOXP3, IL-10, or TGF-beta positive cells in peribronchovascular areas and assessed FOXP3 and IL-10 expression through double-label immunofluorescence. Additionally, we evaluated the gene expression of NF-kappa B and TNF in bronchiolar epithelial cells. Results Our CS-induced COPD model exhibited an increased proinflammatory immune response (increased expression of the NF-kappa B, TNF-alpha, CD4, CD8, CD20, IL-17, and IL-6 markers) with a concomitantly decreased anti-inflammatory immune response (FOXP3, IL-10, and TGF-beta markers) compared with the control mice. These changes in the immune responses were associated with increased alveolar enlargement and impaired lung function starting on the first month and third month of CS exposure, respectively, compared with the control mice. Conclusion Our results showed that the microenvironmental stimuli produced by the release of cyto-kines during COPD progression lead to a Th17/Treg imbalance.
Palavras-chave
Referências
- Baraldo S, 2008, EUR RESPIR J, V31, P486, DOI 10.1183/09031936.00000608
- Barcelo B, 2008, EUR RESPIR J, V31, P555, DOI 10.1183/09031936.00010407
- Brereton CF, 2011, J IMMUNOL, V186, P5896, DOI 10.4049/jimmunol.1003789
- Brusselle GG, 2011, LANCET, V378, P1015, DOI 10.1016/S0140-6736(11)60988-4
- Chen K, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0020333
- Chen WJ, 2003, CYTOKINE GROWTH F R, V14, P85, DOI 10.1016/S1359-6101(03)00003-0
- Chu SY, 2011, INT IMMUNOPHARMACOL, V11, P1780, DOI 10.1016/j.intimp.2011.06.010
- Di Stefano A, 2009, CLIN EXP IMMUNOL, V157, P316, DOI 10.1111/j.1365-2249.2009.03965.x
- Duan MC, 2016, INFLAMMATION, V39, P1334, DOI 10.1007/s10753-016-0365-8
- Eppert BL, 2013, J IMMUNOL, V190, P1331, DOI 10.4049/jimmunol.1202442
- Fuke S, 2004, AM J RESP CELL MOL, V31, P405, DOI 10.1165/rcmb.2004.0131OC
- GOLD, 2018, GLOBAL STRATEGY DIAG
- Gomes RFM, 2000, J APPL PHYSIOL, V89, P908
- Gosman MME, 2006, EUR RESPIR J, V27, P60, DOI 10.1183/09031936.06.00007005
- HANTOS Z, 1992, J APPL PHYSIOL, V72, P168
- Hiemstra PS, 2015, EUR RESPIR J, V45, P1150, DOI 10.1183/09031936.00141514
- Hizume DC, 2012, RESP PHYSIOL NEUROBI, V181, P167, DOI 10.1016/j.resp.2012.03.005
- Hogg JC, 2004, NEW ENGL J MED, V350, P2645, DOI 10.1056/NEJMoa032158
- Jin Y, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0111044
- Kimura A, 2010, EUR J IMMUNOL, V40, P1830, DOI 10.1002/eji.201040391
- Kurimoto E, 2013, RESP RES, V14, DOI 10.1186/1465-9921-14-5
- Le Rouzic O, 2017, EUR RESPIR J, V50, DOI 10.1183/13993003.02434-2016
- Li HJ, 2015, AM J MED SCI, V349, P392, DOI 10.1097/MAJ.0000000000000447
- Livak KJ, 2001, METHODS, V25, P402, DOI 10.1006/meth.2001.1262
- MARGRAF LR, 1991, AM REV RESPIR DIS, V143, P391
- Mathers CD, 2006, PLOS MED, V3, DOI 10.1371/journal.pmed.0030442
- Pabst R, 2002, J ALLERGY CLIN IMMUN, V110, P209, DOI 10.1067/mai.2002.126836
- Rahman MS, 2005, CLIN IMMUNOL, V115, P268, DOI 10.1016/j.clin.2005.01.014
- Roos AB, 2015, AM J RESP CRIT CARE, V192, P428, DOI 10.1164/rccm.201409-1689OC
- Sales DS, 2017, COPD, V14, P533, DOI 10.1080/15412555.2017.1346069
- Shaykhiev R, 2013, GERONTOLOGY, V59, P481, DOI 10.1159/000354173
- Sinden NJ, 2010, THORAX, V65, P930, DOI 10.1136/thx.2009.130260
- Smolonska J, 2009, AM J RESP CRIT CARE, V180, P618, DOI 10.1164/rccm.200905-0722OC
- Smyth LJC, 2007, CHEST, V132, P156, DOI 10.1378/chest.07-0083
- Toledo AC, 2012, EUR RESPIR J, V39, P254, DOI 10.1183/09031936.00003411
- Toumpanakis D, 2010, AM J RESP CRIT CARE, V182, P1129, DOI 10.1164/rccm.201001-0116OC
- Tsoumakidou M, 2011, CURR DRUG TARGETS, V12, P450, DOI 10.2174/138945011794751546
- van der Strate BWA, 2006, AM J RESP CRIT CARE, V173, P751, DOI 10.1164/rccm.200504-594OC
- Wang HY, 2015, CLIN RESPIR J, V9, P330, DOI 10.1111/crj.12147
- Wang HY, 2012, INT IMMUNOPHARMACOL, V14, P504, DOI 10.1016/j.intimp.2012.09.011
- Weaver CT, 2009, NAT REV IMMUNOL, V9, P883, DOI 10.1038/nri2660
- WEIBEL ER, 1963, LAB INVEST, V12, P131
- Zhu XH, 2009, J IMMUNOL, V182, P3270, DOI 10.4049/jimmunol.0802622
Coleções
Artigos e Materiais de Revistas Científicas - FM/MPT
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/02
Artigos e Materiais de Revistas Científicas - LIM/05
Artigos e Materiais de Revistas Científicas - LIM/12
Carregar mais Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/02
Artigos e Materiais de Revistas Científicas - LIM/05
Artigos e Materiais de Revistas Científicas - LIM/12