Fig. 2. IL-1 and PGE₂ mediate GRO-α, IL-6 and IL-8, but not RANTES induction in carcinoma cell-MSC coculture.

(A) Levels of PGE₂ and the cytokines were measured in CM from the cultures. Data are means ± SE, n = 3. **p < 0.01, ***p < 0.005 (vs that in MSC culture). (B) mRNA levels of the enzymes governing PGE₂ production and the cytokines (upper panel) and COX2 protein levels (lower panel) in MSCs treated with IL-1 as indicated. Data are means ± SE, n = 3. *p < 0.05, **p < 0.01, ***p < 0.005 (vs control). (C) Cytokine levels in CM from MSCs, LoVo cells and LoVoMSC cocultures, in the presence of indomethacin (indo; 100 µM), PGE₂ (100 nM), or Indo + PGE₂. Data are means ± SE, n = 3. (D) IL-6, IL-8 and Gro-α mRNA induction in MSCs either by LoVoCM or by IL-1 in the presence of EP2 and EP4 antagonists (AH6809 15 µM + GW627368X 20 µM). mRNA levels are set as 0% for vehicle-treated MSCs and 100% for LoVoCM-treated or IL-1-treated MSCs. Data are means ± SE, n = 3. *p < 0.05, **p < 0.01 (vs MSC treated with LoVoCM or IL-1 without inhibitors). (E) The proposed interactions for PGE₂ and cytokine induction from MSCs. AA: arachidonic acid.