Anti-IL17 treatment controls airway asthmatic responses exacerbated by LPS

Autor: Maria J. Alonso, Luciana Aristóteles, Carla Máximo Prado, Flavia Ribas, Edna A. Leick, Renato Fragar, Iolanda F.L.C. Tibério, Tabata Maruyama, Maysa Mariana Cruz, Milton A. Martins, Leandro do Nascimento Camargo, Silvia Fukuzaki
Rok vydání: 2017
Předmět:
Zdroj: Airway Pharmacology and Treatment.
Popis: Aims: Studies suggest that IL17 modulates inflammatory and infectious responses. Objectives: To evaluate anti-IL17 treatment in an asthma animal model exacerbated by LPS. Methods: we studied hyperresponsiveness, inflammation, NO-arginase and oxidative stress pathways, remodeling, Rho-kinase 1 and 2, arginase 1 and NFKB in airways of 36 BALB/c male mice repeatedly exposed to ovalbumin and treated or not with anti IL17. Twenty-four hours before the end of experimental protocol a group received LPS (5mg/kg). Results: OVA-LPS-antiIL17 showed: decrease in %Ers-Mch(47.3±4.2cmH 2 O/L/s), %Rrs-Mch(36.7±4.2cmH2O/L/s), eosinophils (7.8±0.4) and neutrophils (1.5±0.2)-10 4 cells/mL in BALF, CD4+(3.1±0.3%), CD8+(2.4±0.3), IL2(1.9±0.1), IL4(4.8±0.7), IL5(3.3±0.7), IL6(2.2±0.3), IL10(2.9±0.3), IL13(14.6±0.9), IL17(5.7±0.9), TNFα(6.3±1.3), MMP9(10.8±1.1), MMP12(3.1±0.5), TIMP1(3.8±0.6), TGFβ1(11.3±1.3), TARC (4.7±0.35), iNOS(5.2±0.5), NFκB(3.4±0.5), Rho-kinase 1(7.8±0.3) Rho-kinase 2(17.9±1.3) positive cells/10 4 μm 2 , collagen fibers subtypes I(22.9±0.6%), collagen fibers III(10.2±1.1%), actin(27.6±3.1%), decorin (2.0±0.5%), lumican(15.9±1.1%), biglican(9.4±0.6%), fibronectin(3.5±0.6%), eotaxin(0.3±0.0%), PGF2α(9.5±0.9%) contents, RT-PCR for IL-6(0.7±0.1) and arginase 1(2.95±1.5) mRNA levels(UA) compared to OVA-LPS (p Conclusions: IL17 is involved in the control of hyperresponsiveness, Th1/Th2/Th17 inflammation, chemokine expression, remodeling, NO-arginase and oxidative stress pathways in an asthma model exacerbated by LPS. These effects are associated to NFkb and Rho-kinase 1 activation. Financial Support: FAPESP, CNPq, LIM-20-HC-FMUSP.
Databáze: OpenAIRE