Mycobacterium tuberculosis subverts negative regulatory pathways in human macrophages to drive immunopathology
Fig 5
The MNK pathway is also a negative regulator of MMP-1 expression.
A. Chemical inhibition of the MNK pathway by MNK-I1 significantly increases MMP-1 secretion from macrophages at 72h. B. Increased MMP-1 secretion is secondary to increased mRNA accumulation at 24h. C. Bone marrow derived macrophages from wild type, MNK1-KO, MNK2-KO or double KO mice were uninfected or infected with Mtb at MOI 1. Supernatants were harvested at 24h, sterile filtered and MMP-3 concentration analyzed by Luminex array. MMP-3 secretion was significantly elevated in the MNK double KO cells. Representative experiment of two each performed in triplicate. D. MNK inhibition suppresses phosphorylation of eIF4E at 180 mins. E. Inhibition of the p90RSK pathway does not significantly change MMP-1 secretion at 72h. A, B: data represent experiments performed in triplicate on a minimum of two occasions, D: 3 separate donors, E: two donors in triplicate. Mean and standard deviation are shown and p values are Student’s t-test.