**2.5 Proteins involving in peritoneal fluid and plasma of endometriosis**

Most of researches have demonstrated that macrophages, lymphocytes, endometrial cells and mesothelial cells are able to produce cytokines and inflammatory mediators such as ILs [3, 46, 47], TNF-a [48], PGF2, PGE2 and thromboxane B2 [49], MCP-1 [50], RANTES [51], eotaxin [52], GROa [47], SDF1 [53], and MIF [50, 54]. The main process is leading to the stimulation of endometriotic cells proliferation and adhesion to ectopic sites, angiogenesis, and stimulation of the release of other cytokines and chemokines, later amplifying their effects.

Macrophages can amplify the activity of COX-2 and PGE2, which results in VEGF stimulation in endothelial cells from endometriotic lesions, together with factor StAR, association with an increased estrogen level in the endometrial tissue [55–57]. PGE2 suppresses the activity of phagocytes, that allowing endometriotic implants formatting [58]. Estrogens and PGE2 can induce FGF-9 expression which can further activate endometrial cells proliferation, paralleling to the stimulation of angiogenesis and apoptosis inhibition at the same time. Lymphocytes are involved in various cytokines production with potential role in endometriosis lesions implanting. Whether in vitro study or in human endometriosis, Th2 cells of peritoneal fluid were shown to stimulate the secretion of IL-4 and IL-10. NK cell-mediated cytotoxicity, commonly manifested by lymphocytes adherence to endometrial cells through LFA-1 — ICAM-1 pathway and their presentation as targets to NK cells, may fail in endometriosis [59, 60]. This indicated the possible mechanism that sICAM-1 may bind to LFA-1 expressing in lymphocytes can prevent endometrial cells recognition involved in endometriosis pathogenesis.

TNF-a is a typical pro-inflammatory cytokine produced by macrophages, which can exhibit high levels in serum and peritoneal fluid of patients with endometriosis [61, 62]. Recent studies have shown that TNF-a-induced activation of IKKb complex leads to the initiation and progression of endometriosis by enhancing the survival rate of ectopic epithelial cells rather than stromal cells and not eutopic epithelial cells [63]. MIF, another cytokine, has been shown a high level in the peritoneal fluid, in serum samples, and in peritoneal macrophages, its secretion being regulated by estrogens in endometriosis [85]. MIF can stimulate endothelial cell proliferation, endometriotic lesions survival, expressing VEGF, IL-8, PGE2, COX-2, MCP-1, aromatase, and resulting back in stimulating TNF-a in endometrial cells [18, 64]. That is why in experimental models, MIF antagonist significantly reduces lesions size of endometriosis by inhibiting cell adhesion, tissue remodeling, angiogenesis, and inflammation, in addition to routine alteration of the balance between pro- and anti-apoptotic factors [65].
