Fig. 2.

Cyclooxygenase 2 (COX2) expressed in macrophages supports intestinal growth. A: photomicrograph of 14-day-old control wild-type (WT) mouse small intestine illustrates expression of COX2 (red) in F4/80- expressing macrophages (green) and in scattered other cells in the lamina propria. COX2^−/− mice had reduced frequency of crypt fission (B), fewer Lgr5⁺ crypt epithelial cells (C), and reduced Lgr5⁺ crypt epithelial stem cell proliferation (D) compared with WT control mice. 16,16-Dimethyl PGE₂ (dmPGE₂) treatment increased epithelial proliferation in COX2^−/− mice as shown by increased frequency of crypt fission (B), increased numbers of Lgr5⁺ cells (C), and increased Lgr5⁺ crypt stem cell proliferation (D). B: WT mice treated with the EP₂ receptor agonist butaprost had increased frequency of crypt fission similar to dmPGE₂ treated mice. WT mice treated with NS-398 had decreased crypt epithelial proliferation as shown by reduced crypt fission (B), decreased numbers of Lgr5⁺ crypt epithelial cells (C), and decreased Lgr5⁺ crypt epithelial stem cell proliferation (D) compared with WT controls. E: positional distribution of BrdU-labeled intestinal crypt epithelial cells in 14-day-old mice. COX2^−/− mice had significantly reduced crypt epithelial cell proliferation in positions 1 to 7 compared with controls. The COX2 specific inhibitor NS-398 reduced crypt epithelial cell proliferation in positions 1 to 6 in WT 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. ^xxP < 0.01 and ^xxxP < 0.001 compared with WT control.