5). In wild type mice with EPA administration, all EPA metabolites were significantly increased compared with wild selleck chemical Lenalidomide type mice without EPA administration. In comparison between wild type and 12/15-LOX-KO mice with EPA administration, 12/15-HEPE was significantly decreased in 12/15-LOX KO mice while PGE3 and 5-HEPE were almost equal amount between wild type and 12/15-LOX-KO mice. Interestingly, EPA-derived bioactive mediators, 18S/R-resolvin E3 (RvE3) which is biosynthesized from 18-HEPE by 12/15-LOX [27], was increased in peritoneal fluids of wild type mice after EPA administration (Fig. 5, center panel). Again, the increase of RvE3 was canceled in 12/15-LOX-KO mice. The other E-series resolvins, RvE1 and RvE2, were negligible amounts in both mice (data not shown).

As for AA metabolites, there was no difference in amounts of AA metabolites between wild type and 12/15-LOX-KO mice after EPA administration. Figure 5 Lipid mediator analyses of peritoneal fluids from wild type or 12/15-LOX-KO mice with or without EPA administration. Comparison of expression profiles in endometriotic lesions between fat-1 and wild type mice In humans, the symptoms of endometriosis are thought to result from an excessive inflammatory environment within the peritoneal cavity. Elevated numbers of activated immune cells, including macrophages, are involved in the production of inflammatory cytokines. The expression profiles of endometriotic lesions in our mice model were assessed using cDNA microarrays.

A comparison was made for the expression of the main cytokines between fat-1 and wild type mice and the ratio of fat-1/wild type for each cytokine was indicated in Table 1 (n=3 in each group). Among the cytokines examined, the IL-6 was the only one which was reduced of a ratio greater than 0.5. Indeed, IL-6 expression in endometriotic lesions of fat-1 mice was one fifth lower than that in wild type mice. Table 1 Comparison of the cytokine/chemokine profiles of peritoneal endometriotic lesions between fat-1 and wild type (WT) mice (n=3 in each group). Suppression of IL-6 mRNA production in peritoneal macrophages in fat-1 mice Peritoneal macrophages are one of the most important immune cells to play a role in the development and progression of endometriosis in the peritoneal cavity.

Interestingly, peritoneal macrophages possess 12/15-LOX abundantly and, in turn, 12/15-LOX expressing cells are predominantly macrophages in the peritoneal cavity in mice, while circulating and myeloid monocytes do not express 12/15-LOX. We focused on peritoneal macrophages as a source of IL-6 and isolated macrophages from the peritoneal Batimastat cavity of fat-1 and wild type mice by CD11b-positive selection. A comparison was made between the fat-1 and wild type mice for IL-6 mRNA expression in peritoneal macrophages (n=5 in each group) (Fig. 6).