%0 Journal Article
%T Pharmacologic inhibition of MEK1/2 reduces lung inflammation without impairing bacterial clearance in experimental Pseudomonas aeruginosa pneumonia
%A Anne M. Manicone
%A Ke-Qin Gong
%A Matthew E. Long
%A W. Conrad Liles
%A William E. Eddy
%J Archive of "Pneumonia".
%D 2017
%R 10.1186/s41479-017-0037-y
%X MEKi delivered after P. aeruginosa infection reduces inflammation without impairing bacterial clearance. C57BL/6J mice were infected with a target inoculum of 5 ¡Á 106 CFU of P. aeruginosa by oropharyngeal instillation. a Animal weight was monitored over 4 days and IP injections of PBS + MEKi or PBS + carrier control were given to groups on days 2 and 3 post-infection. Mice receiving MEKi had significantly reduced weight loss on day 3 compared to carrier-treated animals, while treatments of uninfected mice did not alter animal weight. Data shown are mean ¡À SEM of 7 mice for each P. aeruginosa infected group from one representative experiment of three; the weights from additional controls of uninfected na£¿ve (n = 4), uninfected carrier-treated (n = 7), and uninfected MEKi-treated (n = 7) are also included in this graph. Two-way ANOVA with Bonferroni¡¯s multiple comparisons was used to analyze results. b Animals were euthanized 4 days after infection and lungs were homogenized in sterile PBS and plated for colony-forming unit (CFU) enumeration. There was no statistical difference in lung CFU between P. aeruginosa infected carrier and MEKi-treated groups (n = 16/group), demonstrating that bacterial clearance was not impaired by MEKi-treatment. c Total BAL cells, neutrophils and macrophages were enumerated and identified on Diff-quick cytospin preparation (n = 16/ P. aeruginosa infected group) and analyzed by parametric unpaired t-test. d Cell-free BALF was used to measure total protein and IgM (carrier n = 12, MEKi n = 11) and were analyzed by nonparametric Mann-Whitney t-test. Error bars show the mean ¡À SEM. *** p < 0.001, **** p < 0.0001, ns not significan
%K Macrophage
%K MEK1/2
%K Pseudomonas aeruginosa
%K Lung
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583963/