Gene expression and functional analysis of Toll-like receptors (TLRs) in endometriosis

• Grant number: 09/50470-8
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2009
• End date: December 31, 2011
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Silvia Regina Rogatto
• Grantee: Silvia Regina Rogatto
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Endometriosis (EDT) affects 5-15% of women in the reproductive period and is characterized by the presence of stroma and/or endometrial glandular epithelium in extra-uterine location, affecting many organs with various degrees of severity. It has been suggested that EDT is a local inflammatory process and that the immune response can play a role in the development and maintenance of endometriotic lesions. IL-12, IL-6, TNF- TNF-α, IL-1, IL-8 and VEGF, previously associated with EDT, are synthesized at the end of the "Toll-like receptors (TLRs) activation cascades. In addition, TLRs are expressed in normal endometrium and can be modulated by ovarian hormones. We hypothesized that TLRs may be differentially expressed and/or activated in EDT and may play a role in its development and progression. Thus, the aim of this study is to evaluate the role of TLRs in EDT. Initially, TLRs(1-10) mRNA expression will be analyzed in paired eutopic and ectopic endometrium from superficial, ovarian and deeply EDT patients compared with normal endometrium. The TLRs levels will be correlated with IL-6, TNF- TNF-α, IL-1, IL-8, VEGF and IL-10 expression. In the second stage, it functional analysis of the relevant TLRs previously identified will be done. Cell cultures derived from normal endometrium and from eutopic and ectopic endometrium from EDT patients will be stimulated with specific TLRs ligands. Cytokines and growth factors produced will be measured. In order to detect the effect of estrogen/progesterone in TLR response, cell cultures will be also incubated in the presence of these hormones. This study opens a new line of research in EDT that can contribute to disease knowledge and ultimately be translated to the clinical practice. (AU)