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

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IL-1 and PGE2 mediate GRO-α, IL-6, and IL-8, but not RANTES induction in carcinoma cell–MSC coculture. 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 conditioned media 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 (top) and COX-2 protein levels (bottom) 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 conditioned media from MSCs, LoVo cells, and LoVo/MSC cocultures, in the presence of indomethacin (indo; 100 μmol/L), PGE2 (100 nmol/L), 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 μmol/L + GW627368X 20 μmol/L). 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. Hua-Jung Li et al. Cancer Discovery 2012;2:840-855 ©2012 by American Association for Cancer Research