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. Author manuscript; available in PMC: 2015 Sep 1.
Published in final edited form as: Autoimmunity. 2014 May 6;47(6):409–418. doi: 10.3109/08916934.2014.914507

Figure 5. MTX synergizes with 1MT by inhibition of folate metabolism.

Figure 5

K/BxN mice were treated with Carrier, MTX alone (1mg/kg), 1MT alone (400mg/kg), or MTX + 1MT from 3–6wk of age. To determine if the synergistic effect of 1MT + MTX was due to increased adenosine release, mice were treated with 1MT and MTX in combination with (A) the adenosine receptor A1, A2a, and A2b antagonist theophylline (10mg/kg, p.o.), n=10 mice per treatment group, or (B) the adenosine receptor A3 agonist IB-MECA (0.5mg/kg, i.p.), n=8 mice per treatment group. (C) To determine if inhibition of polyamine synthesis could mimic the effect of MTX, mice were treated with 1MT together with the ODC inhibitor DMFO (1% in drinking water), n=9 mice per treatment group. (D) To test whether inhibition of folate metabolism was responsible for the synergistic effect of 1MT + MTX, 1MT + MTX treatment was supplemented with folinic acid (25mg/kg, p.o.), n=10 mice per treatment group. The graphs show mean ankle thickness ± SEM for the indicated number of mice per treatment group pooled from two independent experiments each. *p<0.05, n.s., not significant.