Effects of VAChT reduction and alpha 7nAChR stimulation by PNU-282987 in lung inflammation in a model of chronic allergic airway inflammation
Carregando...
Citações na Scopus
12
Tipo de produção
article
Data de publicação
2020
Título da Revista
ISSN da Revista
Título do Volume
Editora
ELSEVIER
Autores
MIRANDA, Claudia J. C. P.
SANTANA, Fernanda R.
BITTENCOURT-MERNAK, Marcia
FESTA, Sergio
CAPERUTO, Luciana C.
Citação
EUROPEAN JOURNAL OF PHARMACOLOGY, v.882, article ID 173239, 16p, 2020
Resumo
The cholinergic anti-inflammatory pathway has been shown to regulate lung inflammation and cytokine release in acute models of inflammation, mainly via alpha 7 nicotinic receptor (alpha 7nAChR). We aimed to evaluate the role of endogenous acetylcholine in chronic allergic airway inflammation in mice and the effects of therapeutic nAChR stimulation in this model. We first evaluated lung inflammation and remodeling on knock-down mice with 65% of vesicular acetylcholine transport (VAChT) gene reduction (KDVAChT) and wild-type(WT) controls that were subcutaneously sensitized and then inhaled with ovalbumin(OVA). We then evaluated the effects of PNU282987(0.5-to-2mg/kg),( alpha 7nAChR agonist) treatment in BALB/c male mice intraperitoneal sensitized and then inhaled with OVA. Another OVA-sensitized-group was treated with PNU-282987 plus Methyllycaconitine (MLA,1 mg/kg, alpha 7nAChR antagonist) to confirm that the effects observed by PNU were due to alpha 7nAChR. We showed that KDVAChT-OVA mice exhibit exacerbated airway inflammation when compared to WT-OVA mice. In BALB/c, PNU-282987 treatment reduced the number of eosinophils in the blood, BAL fluid, and around airways, and also decreased pulmonary levels of IL-4,IL-13,IL-17, and IgE in the serum of OVA-exposed mice. MLA pretreatment abolished all the effects of PNU-282987. Additionally, we showed that PNU-282987 inhibited STAT3phosphorylation and reduced SOCS3 expression in the lung. These data indicate that endogenous cholinergic tone is important to control allergic airway inflammation in a murine model. Moreover, alpha 7nAChR is involved in the control of eosinophilic inflammation and airway remodeling, possibly via inhibition of STAT3/SOCS3 pathways. Together these data suggest that cholinergic anti-inflammatory system mainly alpha 7nAChR should be further considered as a therapeutic target in asthma.
Palavras-chave
Vesicular acetylcholine transporter, Chronic allergic airway inflammation, a7 nicotinic acetylcholine
Referências
- Antunes GL, 2020, J CELL PHYSIOL, V235, P1838, DOI 10.1002/jcp.29101
- Araujo BB, 2008, EUR RESPIR J, V32, P61, DOI 10.1183/09031936.00147807
- Blanchet MR, 2007, J LEUKOCYTE BIOL, V81, P1245, DOI 10.1189/jlb.0906548
- Blanchet MR, 2005, EUR RESPIR J, V26, P21, DOI 10.1183/09031936.05.00116104
- Bodnar AL, 2005, J MED CHEM, V48, P905, DOI 10.1021/jm049363q
- Chatterjee PK, 2009, AM J PHYSIOL-CELL PH, V297, pC1294, DOI 10.1152/ajpcell.00160.2009
- Chetta A, 1997, CHEST, V111, P852, DOI 10.1378/chest.111.4.852
- Conrad M.L., 2009, CLIN EXP ALLERGY, DOI [10.1111/j.1365-2222.2009, DOI 10.1111/J.1365-2222.2009]
- de Castro BM, 2009, MOL CELL BIOL, V29, P5238, DOI 10.1128/MCB.00245-09
- de Jonge WJ, 2005, NAT IMMUNOL, V6, P844, DOI 10.1038/ni1229
- dos Santos TM, 2018, FRONT PHYSIOL, V9, DOI 10.3389/fphys.2018.01183
- Dullaers M, 2017, J ALLERGY CLIN IMMUN, V140, P76, DOI 10.1016/j.jaci.2016.09.020
- Fukaya Y, 1996, AM J PHYSIOL-HEART C, V270, pH99
- Galle-Treger L, 2016, NAT COMMUN, V7, DOI 10.1038/ncomms13202
- Gallowitsch-Puerta M, 2005, ANN NY ACAD SCI, V1062, P209, DOI 10.1196/annals.1358.024
- Global Initiative for Asthma, 2019, GLOB STRAT ASTHM MAN
- Greenlee K.J., 2013, KENDRA, V71, P233, DOI [10.1038/mp.2011.182, DOI 10.1038/MP.2011.182]
- Halwani R, 2010, CURR OPIN PHARMACOL, V10, P236, DOI 10.1016/j.coph.2010.06.004
- Hasegawa T, 2017, EUR CYTOKINE NETW, V28, P8, DOI 10.1684/ecn.2017.0390
- Horiguchi K, 2009, J NEUROSCI RES, V87, P2740, DOI 10.1002/jnr.22102
- Ikarashi Y, 1998, NEUROCHEM INT, V33, P255, DOI 10.1016/S0197-0186(98)00029-1
- Ishii M, 2006, CURR PHARM DESIGN, V12, P3573, DOI 10.2174/138161206778522056
- Jeremias IC, 2016, MOL NEUROBIOL, V53, P6635, DOI 10.1007/s12035-015-9538-y
- Jiang YL, 2014, CELL PHYSIOL BIOCHEM, V33, P389, DOI 10.1159/000356678
- Kawashima K, 2007, LIFE SCI, V80, P2314, DOI 10.1016/j.lfs.2007.02.036
- Leite HR, 2016, BRAIN BEHAV IMMUN, V57, P282, DOI 10.1016/j.bbi.2016.05.005
- Lemanske RF, 2010, J ALLERGY CLIN IMMUN, V125, pS95, DOI 10.1016/j.jaci.2009.10.047
- Lemjabbar H, 1999, AM J RESP CRIT CARE, V159, P1298, DOI 10.1164/ajrccm.159.4.9708080
- Lima R.deF., 2010, J NEUROCHEM, V71, P233, DOI [10.1038/mp.2011.182, DOI 10.1038/MP.2011.182]
- Lips KS, 2007, LIFE SCI, V80, P2263, DOI 10.1016/j.lfs.2007.01.026
- Lips KS, 2005, AM J RESP CELL MOL, V33, P79, DOI 10.1165/rcmb.2004-0363OC
- Maouche K, 2009, AM J PATHOL, V175, P1868, DOI 10.2353/ajpath.2009.090212
- Mishra NC, 2008, J IMMUNOL, V180, P7655, DOI 10.4049/jimmunol.180.11.7655
- Murphy DM, 2010, CHEST, V137, P1417, DOI 10.1378/chest.09-1895
- Pavlov V.A., 2006, CONTROLLING INFLAMMA, P1037
- Pena G, 2010, J MOL MED, V88, P851, DOI 10.1007/s00109-010-0628-z
- Peng GY, 2010, J IMMUNOL, V184
- Pinheiro NM, 2017, FASEB J, V31, P320, DOI 10.1096/fj.201600431R
- Pinheiro NM, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0120441
- Pitsikas N, 2009, BEHAV BRAIN RES, V200, P160, DOI 10.1016/j.bbr.2009.01.014
- Possa SS, 2013, FRONT PHARMACOL, V4, DOI 10.3389/fphar.2013.00046
- Prado CM, 2006, AM J RESP CELL MOL, V35, P457, DOI 10.1165/rcmb.2005-0391OC
- Prado MAM, 2002, NEUROCHEM INT, V41, P291, DOI 10.1016/S0197-0186(02)00044-X
- Prado VF, 2006, NEURON, V51, P601, DOI 10.1016/j.neuron.2006.08.005
- Proskocil BJ, 2004, ENDOCRINOLOGY, V145, P2498, DOI 10.1210/en.2003-1728
- Racke K, 2006, EUR J PHARMACOL, V533, P57, DOI 10.1016/j.ejphar.2005.12.050
- Roy A, 2013, FASEB J, V27, P5072, DOI 10.1096/fj.13-238279
- Santana FPR, 2019, ECOTOX ENVIRON SAFE, V167, P494, DOI 10.1016/j.ecoenv.2018.10.005
- Seki Y, 2003, NAT MED, V9, P1047, DOI 10.1038/nm896
- Shao ZZ, 2019, MOL MED REP, V19, P3791, DOI 10.3892/mmr.2019.10016
- Simeone-Penney M.C., 2007, J IMMUNOL
- Su X, 2007, AM J RESP CELL MOL, V37, P186, DOI 10.1165/rcmb.2006-0240OC
- Toledo AC, 2013, BRIT J PHARMACOL, V168, P1736, DOI 10.1111/bph.12062
- van Westerloo DJ, 2010, WIEN MED WOCHENSCHR, V160, P112, DOI 10.1007/s10354-010-0761-x
- Verbout NG, 2009, AM J PHYSIOL-LUNG C, V297, pL228, DOI 10.1152/ajplung.90540.2008
- Vieira RP, 2007, AM J RESP CRIT CARE, V176, P871, DOI 10.1164/rccm.200610-1567OC
- Weibel E.R., 1963, LAB INVEST
- Yamada M, 2018, FRONT PHARMACOL, V9, DOI 10.3389/fphar.2018.01426
- Yin YL, 2015, HUM IMMUNOL, V76, P775, DOI 10.1016/j.humimm.2015.09.037
- Yu M, 2018, J ALLERGY CLIN IMMUN, V142, P1618, DOI 10.1016/j.jaci.2018.04.001
- Zar HJ, 2012, PEDIATR DRUGS, V14, P353, DOI 10.2165/11597420-000000000-00000