Fig. 6: Decorin suppresses Nf1-OPG formation through microglia NFkB inhibition.

a Nf1^OPG mouse optic nerves (n = 3) have increased Iκbα phosphorylation relative to WT mice (n = 3). b The increased Iκbα phosphorylation in PBS-treated Nf1^OPG mouse optic nerves (n = 3) was reduced by OVA treatment (n = 3). c Activated TCM (act-Tm) increased Iκbα phosphorylation in microglia, which was reduced following the addition of decorin (800 pg/ml). d Decorin (800 pg/ml) blocks the increased p65-NFκB Ser⁵³⁶ phosphorylation induced by activated TCM (act-Tm) treatment (n = 3). e Decorin (800 pg/ml) blocks the increased total p65-NFκB expression, (f) as well as the nuclear localization of p65-NFκB, induced by activated TCM (act-Tm) treatment (n = 3). β-actin and HDAC are used as controls for total protein expression and the nuclear fractions, respectively. g Schematic representation of the NFκB inhibitor treatment used. Nf1^OPG mice were treated between 4 and 6 weeks of age with the CAPE NFκB inhibitor (n = 8), whereas control Nf1^OPG mice received PBS only (n = 8). Isolated optic nerves were analyzed at 12 weeks of age. h NFκB inhibitor treatment reduced optic glioma volume and (i) proliferation (%Ki67⁺ cells), as well as microglia (%Iba1⁺ cells) and T-cell (CD3⁺) content within the optic nerves of Nf1^OPG mice relative to vehicle-treated controls. Two-tailed Student’s t test. j Reduced Ccl5 RNA expression was observed in the optic nerves from Nf1^OPG mice treated with the CAPE NFκB inhibitor (NFκB-IN) (n = 5). Two-tailed Student’s t test. k Proposed model of asthma-induced decorin suppression of the Nf1^OPG neuron-immune-cancer cell axis. Asthma induces T cell production of decorin, which reduces T cell Ccl4-mediated microglia Ccl5 expression through inhibition of NFκB signaling. Data are presented as the means ± SEM. Exact P values are indicated within each panel. i Scale bars 40 µm. From left to right in each panel: h P = 0.0288; i P = 0.0003, P = 0.0196, P = 0.0025; j P = 0.0018.