Effects of tumor necrosis factor‐α on cell proliferation, prostaglandins and matrix‐metalloproteinases production in rat endometrial stromal cells cultured in vitro

Abstract

Tumor necrosis factor-alpha (TNF-alpha) is known as a pluripotent cell mediator, and it is implicated in the control of uterine cell growth, differentiation and function during estrous cycle and pregnancy. In this study, we investigated the effect of TNF-alpha on endometrial stromal cells derived from rat uterus (rat endometrial stromal cells, RES). RES were isolated from rat endometrium at day 5 of pregnancy. Proliferation activities of RES were measured by using bromodeoxyuridine (BrdU) labeling kit, the productions of prostaglandin E2 (PGE2) and prostaglandin F2alpha (PGF2alpha) were measured by enzyme immunoassay kits and the production of matrix metalloproteinases (MMPs) was analyzed by gelatin-zymography. TNF-alpha, as well as epidermal growth factor and fibroblast growth factor-2, significantly increased the proliferation activity of RES (P<0.05). TNF-alpha selectively stimulated the production of PGE2 in RES (P<0.05), but not the production of PGF2alpha. Additionally, TNF-alpha did not stimulate the production of MMPs in RES at the concentration of 5 ng/mL, compared with the control groups (P>0.05). In conclusion, this study demonstrates several regulational functions of TNF-alpha on RES using in vitro culture system. The effects of TNF-alpha on proliferation and MMP production of RES have been shown for the first time. We believe that these results demonstrate part of the functions of TNF-alpha in endometrium and contribute to the better understanding of endometrial functions.

Influence of anabolic combinations of an androgen plus an estrogen on biochemical pathways in bovine uterine endometrium and ovary

“…Our data suggest that AR is targeted by anabolic steroids in bovine uterus and ovary triggering cell growth. Concordantly, TNF␣, CEBPD and c-fos, which were shown to be implicated in cell turnover under the influence of steroid hormones [9,10,12,31,32], were up-regulated in Nguni heifers indicating a higher proliferation rate. While cell growth was induced, a parallel inhibition of apoptotic and tissue degrading factors occurred.…”

Tumor Necrosis Factor-alpha as a possible auto-/paracrine factor affecting estrous cycle in the cat uterus

“…TNFα/TNFR1 complex has been demonstrated to activate PLA2 and, hence, increase PG secretion (Clark et al 1988). In the rat endometrium, TNFα affected both PGE 2 (Gamo et al 2007), and PGF 2α (Arslann and Zingg 1996). Murakami et al (2001) provided arguments that TNFα affects both PGF 2α and PGE 2 in the bovine endometrium and this action is strongly related to the stage of the estrous cycle.…”

“…TNFα messenger RNA and protein has been shown in amniotic fluid, placenta and blastocysts, and thus TNFα participation in embryonic development and early pregnancy has been proven (Hunt et al 1996). TNFα has been reported to augment PG secretion in the uterus of humans (Chen et al 1995) and several other investigated animals , Blitek and Ziecik 2006, Gamo et al 2007). In the uterus, under pathologic conditions, contaminating bacteria interact with germ-line-en-coded pattern recognition receptors (Toll-like receptors, TLRs) and thereby initiate a cascade of signaling events that include an early inflammatory response (Horne et al 2008), such as a stimulation of TNFα production (Sheldon and Dobson 2004).…”

Expression of peroxisome proliferator-activated receptor isoforms in the rat uterus during early pregnancy

“…Preparation and culture of cells Preparation and culture of cells were performed according to our previous method (Gamo et al 2007). In brief, rat endometrial stromal cells (RES) were isolated from uterine horns of the pregnant rats on 4.5 dpc.…”