Abstract
Endometriosis is caused by the displacement of endometrium outside the uterus contributing heavily to infertility and debilitating pelvic pain. Ectopic adhesion and growth are believed to occur under the influence of a favorable hormonal environment and immunological factors. The objective of this study is to analyze the effect of a targeted therapy with an antibody-based pharmacodelivery of interleukin 4 (F8-IL4) in a mouse model of experimentally induced endometriosis. Endometriosis-like lesions were induced in Balb/c mice. The animals were treated intravenously with F8-IL4 or with untargeted IL4 (KSF-IL4). Twelve days after disease induction, the lesions were isolated. A significant reduction in the number of total lesions/mouse and in the total volume of lesions/mouse was observed in mice treated with F8-IL4 compared to controls (P =.029 and P =.006, respectively), while no difference was found between KSF-IL4-treated mice and their controls. Gene expression was evaluated by quantitative real-time polymerase chain reaction. Expression of genes involved in cell adhesion, extracellular matrix invasion, and neovascularization was significantly downregulated in F8-IL4-treated mice compared to their controls (integrin β1: P =.02; metalloproteinase [MMP] 3: P =.02; MMP9: P =.04; vascular endothelial growth factor: P =.04). Gene expression of inflammatory cytokines (tumor necrosis factor α, IL1β, IL1α, and IL6) did not vary in the ectopic lesions isolated from F8-IL4-treated mice compared to their controls. Immunohistochemistry demonstrated a significantly reduced expression of E-cadherin and β-catenin in the lesions of mice treated with F8-IL4. Our results show that the antibody-mediated targeted delivery of IL4 inhibits the development of endometriosis in a syngeneic mouse model by likely impairing adhesion, invasion, and vascularization of the ectopic endometrium.
| Original language | English |
|---|---|
| Pages (from-to) | 1143-1152 |
| Number of pages | 10 |
| Journal | Reproductive Sciences |
| Volume | 22 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sep 12 2015 |
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Keywords
- endometriosis
- IL-4
- immunocytokine
ASJC Scopus subject areas
- Obstetrics and Gynaecology
Cite this
The Targeted Delivery of Interleukin 4 Inhibits Development of Endometriotic Lesions in a Mouse Model. / Quattrone, Federica; Sanchez, Ana Maria; Pannese, Maria; Hemmerle, Teresa; Viganò, Paola; Candiani, Massimo; Petraglia, Felice; Neri, Dario; Panina-Bordignon, Paola.
In: Reproductive Sciences, Vol. 22, No. 9, 12.09.2015, p. 1143-1152.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The Targeted Delivery of Interleukin 4 Inhibits Development of Endometriotic Lesions in a Mouse Model
AU - Quattrone, Federica
AU - Sanchez, Ana Maria
AU - Pannese, Maria
AU - Hemmerle, Teresa
AU - Viganò, Paola
AU - Candiani, Massimo
AU - Petraglia, Felice
AU - Neri, Dario
AU - Panina-Bordignon, Paola
PY - 2015/9/12
Y1 - 2015/9/12
N2 - Endometriosis is caused by the displacement of endometrium outside the uterus contributing heavily to infertility and debilitating pelvic pain. Ectopic adhesion and growth are believed to occur under the influence of a favorable hormonal environment and immunological factors. The objective of this study is to analyze the effect of a targeted therapy with an antibody-based pharmacodelivery of interleukin 4 (F8-IL4) in a mouse model of experimentally induced endometriosis. Endometriosis-like lesions were induced in Balb/c mice. The animals were treated intravenously with F8-IL4 or with untargeted IL4 (KSF-IL4). Twelve days after disease induction, the lesions were isolated. A significant reduction in the number of total lesions/mouse and in the total volume of lesions/mouse was observed in mice treated with F8-IL4 compared to controls (P =.029 and P =.006, respectively), while no difference was found between KSF-IL4-treated mice and their controls. Gene expression was evaluated by quantitative real-time polymerase chain reaction. Expression of genes involved in cell adhesion, extracellular matrix invasion, and neovascularization was significantly downregulated in F8-IL4-treated mice compared to their controls (integrin β1: P =.02; metalloproteinase [MMP] 3: P =.02; MMP9: P =.04; vascular endothelial growth factor: P =.04). Gene expression of inflammatory cytokines (tumor necrosis factor α, IL1β, IL1α, and IL6) did not vary in the ectopic lesions isolated from F8-IL4-treated mice compared to their controls. Immunohistochemistry demonstrated a significantly reduced expression of E-cadherin and β-catenin in the lesions of mice treated with F8-IL4. Our results show that the antibody-mediated targeted delivery of IL4 inhibits the development of endometriosis in a syngeneic mouse model by likely impairing adhesion, invasion, and vascularization of the ectopic endometrium.
AB - Endometriosis is caused by the displacement of endometrium outside the uterus contributing heavily to infertility and debilitating pelvic pain. Ectopic adhesion and growth are believed to occur under the influence of a favorable hormonal environment and immunological factors. The objective of this study is to analyze the effect of a targeted therapy with an antibody-based pharmacodelivery of interleukin 4 (F8-IL4) in a mouse model of experimentally induced endometriosis. Endometriosis-like lesions were induced in Balb/c mice. The animals were treated intravenously with F8-IL4 or with untargeted IL4 (KSF-IL4). Twelve days after disease induction, the lesions were isolated. A significant reduction in the number of total lesions/mouse and in the total volume of lesions/mouse was observed in mice treated with F8-IL4 compared to controls (P =.029 and P =.006, respectively), while no difference was found between KSF-IL4-treated mice and their controls. Gene expression was evaluated by quantitative real-time polymerase chain reaction. Expression of genes involved in cell adhesion, extracellular matrix invasion, and neovascularization was significantly downregulated in F8-IL4-treated mice compared to their controls (integrin β1: P =.02; metalloproteinase [MMP] 3: P =.02; MMP9: P =.04; vascular endothelial growth factor: P =.04). Gene expression of inflammatory cytokines (tumor necrosis factor α, IL1β, IL1α, and IL6) did not vary in the ectopic lesions isolated from F8-IL4-treated mice compared to their controls. Immunohistochemistry demonstrated a significantly reduced expression of E-cadherin and β-catenin in the lesions of mice treated with F8-IL4. Our results show that the antibody-mediated targeted delivery of IL4 inhibits the development of endometriosis in a syngeneic mouse model by likely impairing adhesion, invasion, and vascularization of the ectopic endometrium.
KW - endometriosis
KW - IL-4
KW - immunocytokine
UR - http://www.scopus.com/inward/record.url?scp=84939183835&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84939183835&partnerID=8YFLogxK
U2 - 10.1177/1933719115578930
DO - 10.1177/1933719115578930
M3 - Article
AN - SCOPUS:84939183835
VL - 22
SP - 1143
EP - 1152
JO - Reproductive Sciences
JF - Reproductive Sciences
SN - 1933-7191
IS - 9
ER -