title: Effects of Rho-kinase inhibition in lung tissue with chronic inflammation.
abstract: We evaluated whether Rho-kinase inhibition (Y-27632) modulated distal lung responsiveness, inflammation, extracellular matrix remodeling and oxidative stress activation in guinea pigs (GPs) with chronic allergic inflammation. GPs were submitted to inhalation of ovalbumin (OVA-2×/week/4 weeks). From the 5th inhalation on, the Rho-kinase inhibitor group animals were submitted to Y-27632 inhalation 10min before each inhalation of OVA. Seventy-two hours after the seventh inhalation, the oscillatory mechanics of the distal lung strips were assessed under the baseline condition and after the ovalbumin challenge. Subsequently, the lung slices were submitted to morphometry. Rho-kinase inhibition in the ovalbumin-exposed animals attenuated distal lung elastance and resistance, eosinophils, IL-2, IL-4, IL-5, IL-13, TIMP-1, MMP-9, TGF-β, IFN-γ, NF-κB and iNOS-positive cells and the volume fraction of 8-iso-PGF2α, elastic, collagen and actin in alveolar walls compared with the OVA group (P<0.05). Rho-kinase inhibition contributed to the control of distal lung responsiveness, eosinophilic and Th1/Th2 responses and extracellular matrix remodeling in an animal model of chronic allergic inflammation.
authors.affiliation: Department of Medicine, School of Medicine, University of São Paulo, 01246-903 São Paulo, Brazil. Electronic address: refragar@gmail.com.
authors.forename: Renato Fraga
authors.initials: RF
authors.lastname: Righetti
authors.affiliation: Department of Medicine, School of Medicine, University of São Paulo, 01246-903 São Paulo, Brazil. Electronic address: pangelipigati@gmail.com.
authors.forename: Patricia Angeli da Silva
authors.initials: PA
authors.lastname: Pigati
authors.affiliation: Department of Medicine, School of Medicine, University of São Paulo, 01246-903 São Paulo, Brazil. Electronic address: szpossa@hotmail.com.
authors.forename: Samantha Souza
authors.initials: SS
authors.lastname: Possa
authors.affiliation: Department of Medicine, School of Medicine, University of São Paulo, 01246-903 São Paulo, Brazil. Electronic address: fabiocetinichabrum@yahoo.com.br.
authors.forename: Fábio Cetinic
authors.initials: FC
authors.lastname: Habrum
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Ilha do Fundão, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. Electronic address: deboraxisto@gmail.com.
authors.forename: Débora Gonçalves
authors.initials: DG
authors.lastname: Xisto
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Ilha do Fundão, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. Electronic address: maryantunes@gmail.com.
authors.forename: Mariana Alves
authors.initials: MA
authors.lastname: Antunes
authors.affiliation: Department of Medicine, School of Medicine, University of São Paulo, 01246-903 São Paulo, Brazil. Electronic address: leick51@yahoo.com.
authors.forename: Edna Aparecida
authors.initials: EA
authors.lastname: Leick
authors.affiliation: Department of Biological Science, Universidade Federal de São Paulo, 09972-270 Diadema, São Paulo, Brazil. Electronic address: cmaximoprado@gmail.com.
authors.forename: Carla Máximo
authors.initials: CM
authors.lastname: Prado
authors.affiliation: Department of Medicine, School of Medicine, University of São Paulo, 01246-903 São Paulo, Brazil. Electronic address: mmartins@usp.br.
authors.forename: Mílton de Arruda
authors.initials: Mde A
authors.lastname: Martins
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Ilha do Fundão, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. Electronic address: prmrocco@gmail.com.
authors.forename: Patrícia Rieken Macedo
authors.initials: PR
authors.lastname: Rocco
authors.affiliation: Department of Medicine, School of Medicine, University of São Paulo, 01246-903 São Paulo, Brazil. Electronic address: iocalvo@uol.com.br.
authors.forename: Iolanda de Fátima Lopes Calvo
authors.initials: Ide F
authors.lastname: Tibério
mesh_terms: D000280:Administration, Inhalation; D000577:Amides / Q000008:administration & dosage; D000704:Analysis of Variance; D000818:Animals; D002908:Chronic Disease; D016207:Cytokines; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006168:Guinea Pigs; D007074:Immunoglobulin G / Q000627:therapeutic use; D008168:Lung / Q000201:enzymology*; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010047:Ovalbumin / Q000009:adverse effects; D011014:Pneumonia / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D011725:Pyridines / Q000008:administration & dosage; D013314:Stress, Mechanical; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D000577:Amides; D016207:Cytokines; D004791:Enzyme Inhibitors; D007074:Immunoglobulin G; D011725:Pyridines; D019715:Tissue Inhibitor of Metalloproteinase-1; C108830:Y 27632; D010047:Ovalbumin; D052247:Nitric Oxide Synthase Type II; D054460:rho-Associated Kinases
keywords: Asthma; Distal lung; Inflammation; Rho-kinase; Y-27632