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Objective: To evaluate the effects of leptin on the production of interleukin (IL)-6 family cytokines and chemokines by human endometrial stromal cells (ESC) and epithelial cells., Design: The effects of leptin on the production of IL-6, IL-11, leukemia inhibitory factor (LIF), IL-8, growth-regulated oncogene (GRO)-alpha, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-3alpha by ESC and the endometrial epithelial cell line HHUA were investigated., Setting: Research laboratory at a medical university., Patient(s): Eight endometrial specimens in the late proliferative phase were used for the isolation of ESC., Intervention(s): ESC and HHUA were incubated for 24 hours with recombinant human leptin., Main Outcome Measure(s): The concentration of IL-6, IL-11, LIF, IL-8, GRO-alpha, MCP-1, and MIP-3alpha were measured using ELISAs., Result(s): Unstimulated ESC and HHUA constitutively secreted IL-6, IL-11, LIF, IL-8, GRO-alpha, MCP-1, and MIP-3alpha. The increase in levels of IL-6, IL-8, GRO-alpha, MCP-1, and MIP-3alpha in the culture media of ESC and HHUA paralleled the addition of increasing amounts of leptin. In contrast, the levels of IL-11 and LIF were not affected by leptin administration., Conclusion(s): The present findings suggest that leptin may be an additional modulator of IL-6 and chemokine expression in the endometrium. Leptin may contribute to the normal and pathological processes of human reproduction by the regulation of these cytokines in the local environment.

Objective: To evaluate the effects of interleukin (IL)-13, a T-helper (Th)2 cytokine, and tumor necrosis factor (TNF)-beta, a Th1 cytokine, on the production of IL-6 family cytokines and chemokines by endometrial stromal cells (ESC)., Design: The effects of IL-13 and TNF-beta, on the production of IL-6, IL-11, leukemia inhibitory factor (LIF), IL-8, growth-regulated oncogene alpha (GROalpha), monocyte chemoattractant protein-1 (MCP-1), regulated on activation, T-cell expressed and secreted (RANTES), and eotaxin were investigated., Setting: Research laboratory at a medical university., Patient(s): Thirteen endometrial specimens in the late proliferative phase were used., Intervention(s): The ESC were incubated for 24 hours with recombinant human IL-13 and recombinant human TNF-beta., Main Outcome Measure(s): The concentration of IL-6, IL-11, LIF, IL-8, GROalpha, MCP-1, RANTES, and eotaxin in the culture media was measured using ELISA., Result(s): The increase in levels of IL-6, IL-8, MCP-1, and eotaxin in the culture media of ESC paralleled the addition of increasing amounts of IL-13 and TNF-beta, whereas the levels of IL-11 and LIF were decreased with increasing amounts of IL-13, but were increased with increasing amounts of TNF-beta. Tumor necrosis factor-beta enhanced the production of GROalpha and RANTES in dose-dependent manner; however, IL-13 did not affect the expression of GROalpha or RANTES., Conclusion(s): These results suggest that IL-13 and TNF-beta secreted in the cyclic endometrial tissue and in the decidua may differentially regulate the production of IL-6 family cytokines and chemokines by ESC. The controlled expression of these cytokines in the endometrium may contribute to the modulation of the immune reaction during the menstrual cycle and in early pregnancy by the regulation of leukocyte trafficking and functions.

PROBLEM: In order to investigate the role of macrophage colony-stimulating factor (M-CSF)and monocyte chemoattractant protein -1 (MCP-1) in human ovulation, we studied the regulation of M-CSF and MCP-1 in cultured human granulosa cells. METHOD OF STUDY: Immortalized granulosa cells (GC1a) were cultured in serum-free medium, and incubated with interleukin (IL)-1α IL-1 receptor antagonist (ra) and tumor necrosis factor (TNF)-α The supernatants were collected, and M-CSF and MCP-1 were measured by ELISA. RESULTS: The levels of M-CSF and MCP-1 were increased after treatment with IL-1α (1 nM and TNF-α (1nM in a time-dependent manner. The levels of M-CSF and MCP-1 were significantly increased after treatment with IL-1α and TNF-α in a dose-dependent manner. However, the levels of M-CSF and MCP-1 were significantly decreased by treatment with IL-1α (1 nM and/or increasing concentrations of IL-1ra. CONCLUSIONS: Our data indicated that M-CSF and MCP-1 were regulated by IL-1α and TNF-α It was suggested that M-CSF and MCP-1 may play an important role in human preovulatory processes. [ABSTRACT FROM AUTHOR]

Hypoxia downregulated the concentration of endostatin in the culture media of human endometrial stromal cells but did not affect the messenger (m)RNA expression of collagen XVIII. Both mRNA and protein expression of vascular endothelial growth factor were upregulated in a hypoxic condition. [Copyright &y& Elsevier]

: ObjectiveTo evaluate the expression of granulocyte chemotactic protein-2 (GCP-2) in human endometrial stromal cells.: DesignThe effects of interleukin (IL)-1α, IL-1β, tumor necrosis factor (TNF)-α, TNF-β, interferon (IFN)-γ, and lipopolysaccharide (LPS) on the production of GCP-2 by endometrial stromal cells were investigated.: SettingResearch laboratory at a medical university.: Patient(s)Eight endometrial specimens in the late proliferative phase were used.: Intervention(s)Endometrial stromal cells were incubated for 24 hours with IL-1α, IL-1β, TNF-α, TNF-β, IFN-γ, and LPS.: Main outcome measure(s)The concentration of GCP-2 in the culture media was measured using an enzyme-linked immunosorbent assay (ELISA).: Result(s)A small amount of GCP-2 was detected in the culture media of unstimulated endometrial stromal cells. The production of GCP-2 by endometrial stromal cells was stimulated with IL-1α, IL-1β, TNF-α, TNF-β, and LPS in a dose-dependent manner. Interferon-γ did not affect GCP-2 production by these cells.: Conclusion(s)These results suggest that GCP-2 is an additional ELR+-CXC chemokine expressed in endometrial stromal cells. The modulation of GCP-2 concentrations in the local environment may contribute to the normal and pathological processes of human reproduction by regulating the neutrophil trafficking in the endometrium. [Copyright &y& Elsevier]

Interferon (IFN)-β, not IFN-α, suppresses vascular endothelial growth factor secretion in endometriotic cyst stromal cells. It was suggested that IFN-β may be more suitable than IFN-α as an anti-endometriotic agent. [Copyright &y& Elsevier]