Objectives:Recurrentpregnancyloss(RPL)isdefinedasthreeor more consecutive miscarriages. Although RPL has been attributed to various anatomic, hematologic, hormonal, immune and genetic defects, in several cases (30–40%), the etiology remains unknown. An abnormal expression of cytokines might be one of the mech anism that adversely affects endometrial receptivity in women with RPL. NALP-3 inflammosome is an intracellular multi-protein complex, belonging to innate immunity system, that, in response to pathogens or cellular danger signals, activates caspase-1 and increases IL-1ß and IL-18 levels. These events are necessary for the induction of further systemic responses and to spreading of inflammation. Aims: To evaluate the expression and activation of NALP-3 inflammosome in endometrial samples from women with unex plained RPL compared to fertile women (controls). Methods: After informed consent, endometrial samples were obtained from 30 women with unexplained RPL and 10 fertile womenundergoing diagnostic mini-invasive hysteroscopy during theimplantationwindow(days19to24).Endometriallysateswere evaluated for NALP-3 inflammosome expression by Western blot analysis and for NALP-3 activation by caspase-1, IL-1ß and IL-18 levels (ELISA). Results: NALP-3 inflammosome expression was increased in endometrial samples obtained from women with RPL compared to controls (p<0.01). The intracellular cascade following NALP-3 assembly was significantly activated in endometrial samples from womenwithRPL, showing increased levels of caspase-1 (p<0.01), IL-1ß and IL-18 (p<0.001), compared to controls. Conclusion: These results demonstrate that endometrial inflammosomeactivationispresentinwomenwithidiopathicRPL. ThehighexpressionofendometrialNALP3andtheincreasedlevels of interleukins in RPL patients support a key role of these pro teins during implantation. Even if further studies are needed, the NALP3 inflammosome might represent a novel family of clinical biomarkers or therapeutic targets in idiopathic RPL.
The inflammosome: A new player from innate immunity in the pathogenesis of recurrent pregnancy loss
N. Di Simone;S. D’Ippolito;
2015-01-01
Abstract
Objectives:Recurrentpregnancyloss(RPL)isdefinedasthreeor more consecutive miscarriages. Although RPL has been attributed to various anatomic, hematologic, hormonal, immune and genetic defects, in several cases (30–40%), the etiology remains unknown. An abnormal expression of cytokines might be one of the mech anism that adversely affects endometrial receptivity in women with RPL. NALP-3 inflammosome is an intracellular multi-protein complex, belonging to innate immunity system, that, in response to pathogens or cellular danger signals, activates caspase-1 and increases IL-1ß and IL-18 levels. These events are necessary for the induction of further systemic responses and to spreading of inflammation. Aims: To evaluate the expression and activation of NALP-3 inflammosome in endometrial samples from women with unex plained RPL compared to fertile women (controls). Methods: After informed consent, endometrial samples were obtained from 30 women with unexplained RPL and 10 fertile womenundergoing diagnostic mini-invasive hysteroscopy during theimplantationwindow(days19to24).Endometriallysateswere evaluated for NALP-3 inflammosome expression by Western blot analysis and for NALP-3 activation by caspase-1, IL-1ß and IL-18 levels (ELISA). Results: NALP-3 inflammosome expression was increased in endometrial samples obtained from women with RPL compared to controls (p<0.01). The intracellular cascade following NALP-3 assembly was significantly activated in endometrial samples from womenwithRPL, showing increased levels of caspase-1 (p<0.01), IL-1ß and IL-18 (p<0.001), compared to controls. Conclusion: These results demonstrate that endometrial inflammosomeactivationispresentinwomenwithidiopathicRPL. ThehighexpressionofendometrialNALP3andtheincreasedlevels of interleukins in RPL patients support a key role of these pro teins during implantation. Even if further studies are needed, the NALP3 inflammosome might represent a novel family of clinical biomarkers or therapeutic targets in idiopathic RPL.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
