Effects of Anti-IL-17 on Inflammation, Remodeling, and Oxidative Stress in an Experimental Model of Asthma Exacerbated by LPS

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Tipo de produção
article
Data de publicação
2018
Título da Revista
ISSN da Revista
Título do Volume
Editora
FRONTIERS MEDIA SA
Citação
FRONTIERS IN IMMUNOLOGY, v.8, article ID 1835, 14p, 2018
Projetos de Pesquisa
Unidades Organizacionais
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Resumo
Inflammation plays a central role in the development of asthma, which is considered an allergic disease with a classic Th2 inflammatory profile. However, cytokine IL-17 has been examined to better understand the pathophysiology of this disease. Severe asthmatic patients experience frequent exacerbations, leading to infection, and subsequently show altered levels of inflammation that are unlikely to be due to the Th2 immune response alone. This study estimates the effects of anti-IL-17 therapy in the pulmonary parenchyma in a murine asthma model exacerbated by LPS. BALB/c mice were sensitized with intraperitoneal ovalbumin and repeatedly exposed to inhalation with ovalbumin, followed by treatment with or without anti-IL-17. Twenty-four hours prior to the end of the 29-day experimental protocol, the two groups received LPS (0.1 mg/ml intratracheal OVA-LPS and OVA-LPS IL-17). We subsequently evaluated bronchoalveolar lavage fluid, performed a lung tissue morphometric analysis, and measured IL-6 gene expression. OVA-LPS-treated animals treated with anti-IL-17 showed decreased pulmonary inflammation, edema, oxidative stress, and extracellular matrix remodeling compared to the non-treated OVA and OVA-LPS groups (p < 0.05). The anti-IL-17 treatment also decreased the numbers of dendritic cells, FOXP3, NF-kappa B, and Rho kinase 1-and 2-positive cells compared to the non-treated OVA and OVA-LPS groups (p < 0.05). In conclusion, these data suggest that inhibition of IL-17 is a promising therapeutic avenue, even in exacerbated asthmatic patients, and significantly contributes to the control of Th1/Th2/Th17 inflammation, chemokine expression, extracellular matrix remodeling, and oxidative stress in a murine experimental asthma model exacerbated by LPS.
Palavras-chave
anti-IL-17, distal lung, asthma, inflammation, LPS-exacerbated
Referências
  1. Abdelmageed ME, 2016, CAN J PHYSIOL PHARM, V94, P140, DOI 10.1139/cjpp-2015-0219
  2. Al-Muhsen S, 2013, RESP RES, V14, DOI 10.1186/1465-9921-14-34
  3. Angeli P, 2008, AM J PHYSIOL-LUNG C, V294, pL1197, DOI 10.1152/ajplung.00199.2007
  4. Arantes-Costa FM, 2008, TOXICOL PATHOL, V36, P680, DOI 10.1177/0192623308317427
  5. Aristoteles LRCRB, 2013, BMC PULM MED, V13, DOI 10.1186/1471-2466-13-52
  6. Bae JS, 2017, ALLERGY ASTHMA IMMUN, V9, P169
  7. Barlow JL, 2011, CLIN EXP ALLERGY, V41, P1447, DOI 10.1111/j.1365-2222.2011.03806.x
  8. Benayoun L, 2003, AM J RESP CRIT CARE, V167, P1360, DOI 10.1164/rccm.200209-1030OC
  9. Chakir J, 2003, J ALLERGY CLIN IMMUN, V111, P1293, DOI 10.1067/mai.2003.1557
  10. Ckless K, 2007, AM J RESP CELL MOL, V36, P645, DOI 10.1165/rcmb.2006-0329SM
  11. Diehl S, 2002, J EXP MED, V196, P39, DOI 10.1084/jem.20020026
  12. Dolhnikoff M, 2009, J ALLERGY CLIN IMMUN, V123, P1090, DOI 10.1016/j.jaci.2009.02.032
  13. Dougherty RH, 2009, CLIN EXP ALLERGY, V39, P193, DOI 10.1111/j.1365-2222.2008.03157.x
  14. Durrant DM, 2010, IMMUNOL INVEST, V39, P526, DOI 10.3109/08820131003615498
  15. Fajt ML, 2017, ALLERGY ASTHMA IMMUN, V9, P3, DOI 10.4168/aair.2017.9.1.3
  16. Fodor RS, 2015, ROM J MORPHOL EMBRYO, V56, P1329
  17. Galli SJ, 2008, NATURE, V454, P445, DOI 10.1038/nature07204
  18. GINA, 2015, GLOB STRAT ASTHM MAN
  19. Gosens R, 2004, EUR J PHARMACOL, V494, P73, DOI 10.1016/j.ejphar.2004.04.035
  20. He WX, 2012, J ENDODONT, V38, P464, DOI 10.1016/j.joen.2011.12.021
  21. Ingram JL, 2015, METALLOPROTEINASES M, V2, P61, DOI [10.2147/MNM.S63614, DOI 10.2147/MNM.S63614]
  22. Kiss T, 2016, BRIT J ANAESTH, V116, P708, DOI 10.1093/bja/aew093
  23. Korn T, 2009, ANNU REV IMMUNOL, V27, P485, DOI 10.1146/annurev.immunol.021908.132710
  24. Krishnan A, 2012, LAB INVEST, V92, P1712, DOI 10.1038/labinvest.2012.121
  25. Kudo M, 2012, NAT MED, V18, P547, DOI 10.1038/nm.2684
  26. Lowe APP, 2015, BRIT J PHARMACOL, V172, P2588, DOI 10.1111/bph.13080
  27. MARGRAF LR, 1991, AM REV RESPIR DIS, V143, P391
  28. Mauad T, 2008, REV PANAM SALUD PUBL, V23, P418, DOI 10.1590/S1020-49892008000600007
  29. Menden HL, 2016, AM J RESP CELL MOL, V55, P767, DOI 10.1165/rcmb.2016-0006OC
  30. Murakami D, 2007, CLIN EXP ALLERGY, V37, P339, DOI 10.1111/j.1365-2222.2006.02633.x
  31. Nakashima AS, 2008, J APPL PHYSIOL, V104, P1778, DOI 10.1152/japplphysiol.00830.2007
  32. Newcomb DC, 2013, CURR OPIN IMMUNOL, V25, P755, DOI 10.1016/j.coi.2013.08.002
  33. Oshita Y, 2003, THORAX, V58, P757, DOI 10.1136/thorax.58.9.757
  34. Overbeek SA, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0055612
  35. Palomares O, 2012, J ALLERGY CLIN IMMUN, V129, P510, DOI 10.1016/j.jaci.2011.09.031
  36. Pantano C, 2008, AM J RESP CRIT CARE, V177, P959, DOI [10.1164/rccm.200707-1096OC, 10.1164/rccm.200707-10960C]
  37. Sakoda CPP, 2016, ACTA HISTOCHEM, V118, P615, DOI 10.1016/j.acthis.2016.07.001
  38. Petroni RC, 2015, INFLAMMATION, V38, P2026, DOI 10.1007/s10753-015-0183-4
  39. Pigati PA, 2015, BMC PULM MED, V15, DOI 10.1186/s12890-015-0073-4
  40. Pinheiro NM, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0120441
  41. Possa SS, 2012, AM J PHYSIOL-LUNG C, V303, pL939, DOI 10.1152/ajplung.00034.2012
  42. Prado CM, 2011, EXP LUNG RES, V37, P259, DOI 10.3109/01902148.2010.538289
  43. Pyzik M, 2007, J LEUKOCYTE BIOL, V82, P335, DOI 10.1189/jlb.1006644
  44. Qin XJ, 2012, ALLERGY, V67, P1547, DOI 10.1111/all.12048
  45. RighettI RF, 2014, RESP PHYSIOL NEUROBI, V192, P134, DOI 10.1016/j.resp.2013.12.012
  46. Rincon M, 2012, INT J BIOL SCI, V8, P1281, DOI 10.7150/ijbs.4874
  47. Rocco PRM, 2003, EUR RESPIR J, V22, P20, DOI 10.1183/09031936.03.00108603
  48. Roussel L, 2010, J IMMUNOL, V184, P4531, DOI 10.4049/jimmunol.0903162
  49. Santos CL, 2017, PLOS ONE, V12, DOI 10.1371/journal.pone.0178207
  50. Seitzman GD, 1998, AM J RESP CELL MOL, V18, P800, DOI 10.1165/ajrcmb.18.6.3063
  51. Starkhammar M, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0032110
  52. Starling CM, 2009, RESP PHYSIOL NEUROBI, V165, P185, DOI 10.1016/j.resp.2008.11.011
  53. Taher YA, 2010, LIBYAN J MED, V5, DOI 10.3402/ljm.v5i0.5303
  54. Tiberio IFLC, 1997, AM J RESP CRIT CARE, V155, P1739, DOI 10.1164/ajrccm.155.5.9154886
  55. Tulic MK, 2003, CHEST, V123, p348S, DOI 10.1378/chest.123.3_suppl.348S
  56. Veldhoen M, 2006, IMMUNITY, V24, P179, DOI 10.1016/j.immuni.2006.01.001
  57. Venancio TM, 2016, MEDIAT INFLAMM, DOI 10.1155/2016/1784014
  58. Wakashin H, 2008, AM J RESP CRIT CARE, V178, P1023, DOI 10.1164/rccm.200801-086OC
  59. Wang YH, 2011, CURR ALLERGY ASTHM R, V11, P388, DOI 10.1007/s11882-011-0210-y
  60. Willis CR, 2015, AM J RESP CELL MOL, V53, P810, DOI 10.1165/rcmb.2015-0038OC
  61. Wilson NJ, 2007, NAT IMMUNOL, V8, P950, DOI 10.1038/ni1497
  62. Zhao Y, 2011, J ASTHMA, V48, P429, DOI 10.3109/02770903.2011.570403