Fig. 3.

Exogenous PGE₂ rescues positional crypt epithelial cell proliferation in mice having reduced proliferation due to macrophage depletion, deletion of Toll-like receptor 4 (TLR4) in macrophage, or deletion of cyclooxygenase 2 (COX2). A: 5-bromo-2-deoxyuridine (BrdU) was administered to mice 90 min before being euthanized. The percentage of epithelial cells that were BrdU labeled was assessed for each epithelial position. 16,16-Dimethyl PGE₂ (dmPGE₂) treatment of wild-type (WT) mice from age 7 days to age 14 days significantly increased epithelial proliferation in positions 1 to 3. In WT mice depleted of macrophages due to treatment with anionic liposomal clodronate, in TLR4^f/fLysM-Cre^+/− mice having constitutive deletion of TLR4 in macrophage, and in COX2^−/− mice there is significantly reduced epithelial cell proliferation in the lower one-half of the intestinal crypt. Simultaneous treatment with dmPGE₂ significantly increased crypt epithelial cell proliferation in all three conditions; positions 1 to 5 in TLR4^f/fLysM-Cre^+/− and macrophage-depleted WT mice and positions 1 to 7 in COX2^−/− mice. Furthermore, in the crypt base, dmPGE₂ increased proliferation at or above that found in WT control mice. Values are means ± SE for 8–15 mice/treatment group. *P < 0.05, **P < 0.01, and ***P < 0.001 compared with control mice of the same genotype. ++P < 0.01 and +++P < 0.001 compared with WT control mice. B: representative histological sections showing BrdU staining.