Abstract
Endometriosis is a female disease in which endometrial tissues grows outside the uterus. Patients showed alterations in endocrine and immune systems. Endometriotic lesions are characterized by deregulated interaction between immune cells and tissue cells. The formyl peptide receptor 1 (Fpr1) is expressed by both immune and stromal cells including epithelial cells. We investigated the development of the physiopathology of the surgically-induced endometriosis in Fpr1 KO mice compared to WT animals. Operated Fpr1 KO mice showed lower duration of uterine pain behaviors, lower size of developed cysts and reduced mast cell numbers. Immunohistochemical analyses indicated changes in NGF, VEGF and ICAM-1 expression associated with the pathology, which were reduced in absence of the Fpr1 gene. Molecular analyses indicated that in absence of Fpr1 there was reduced neutrophils accumulation and nitrosative stress formation, NF-κB translocation into the nucleus as well as NRLP3 inflammasome signalling. Fpr1 gene deletion caused reduction of resistance to the apoptosis, assessed by TUNEL assay. We underline the pathogenic role of Fpr1 in experimental endometriosis, which is the result of modulation of immune cell recruitment, suggesting it as a new target to control the pathologic features of endometriotic lesions.
Highlights
Endometriosis is a debilitating disease which affects reproductive-age women
WT (Figure 1D) and formyl peptide receptor 1 (Fpr1) KO (Figure 1E) mice did not showed a different number of cyst, but cyst size was smaller in Fpr1 KO mice compared to control animals (P < 0.05) (Figure 1F)
Implantation, proliferation, angiogenesis, and inflammation play a central role in the initiation and growth of endometriotic lesions: in the present study we showed that the absence of Fpr1 was able to reduce cyst diameter and histopathological score of endometriosis and to ameliorate the suffering induced by the disease
Summary
Endometriosis is a debilitating disease which affects reproductive-age women. It is characterized by the attendance of endometrial glands and stroma outside the uterus. Mouse neutrophils express orthologous of human Fpr and Fpr2 [12, 13] This two receptors can bind some pro-inflammatory peptides with chemotactic activity and release reactive oxygen species (ROS) and granule constituents from immune cells [14, 15]. In particular it has been described the up-regulation of the Fpr in patients affected by endometriosis and its role in cell differentiation and proliferation [16]. Of these NLR Family Pyrin Domain Containing 3 (NLRP3) is the most characterized The activation of this inflammasome complex has been described in the physiopathology of the endometriosis [17], in association with chronic pain as well [18]. Considering the multifactorial and complex pathogenesis of the endometriosis, in this paper, we investigate how gene deletion of mouse Fpr can impact on the macropscopic and microscopic features of the endometriosis, leading to an outcome related with a modulation of inflammasome signalling in the injured tissue
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