TY - JOUR T1 - Pre-eclampsia affects procalcitonin production in placental tissue. JF - Am J Reprod Immunol Y1 - 2018 A1 - Agostinis, Chiara A1 - Rami, Damiano A1 - Zacchi, Paola A1 - Bossi, Fleur A1 - Stampalija, Tamara A1 - Mangogna, Alessandro A1 - Amadio, Leonardo A1 - Vidergar, Romana A1 - Vecchi Brumatti, Liza A1 - Ricci, Giuseppe A1 - Celeghini, Claudio A1 - Radillo, Oriano A1 - Sargent, Ian A1 - Bulla, Roberta KW - Adult KW - Calcitonin KW - Cohort Studies KW - Female KW - Humans KW - Macrophages KW - Placenta KW - Pre-Eclampsia KW - Pregnancy KW - Trophoblasts KW - Tumor Necrosis Factor-alpha KW - Up-Regulation KW - Young Adult AB -

PROBLEM: Procalcitonin (PCT) is the prohormone of calcitonin which is usually released from neuroendocrine cells of the thyroid gland (parafollicular) and the lungs (K cells). PCT is synthesized by almost all cell types and tissues, including monocytes and parenchymal tissue, upon LPS stimulation. To date, there is no evidence for PCT expression in the placenta both in physiological and pathological conditions.

METHOD: Circulating and placental PCT levels were analysed in pre-eclamptic (PE) and control patients. Placental cells and macrophages (PBDM), stimulated with PE sera, were analysed for PCT expression. The effect of anti-TNF-α antibody was analysed.

RESULTS: Higher PCT levels were detected in PE sera and in PE placentae compared to healthy women. PE trophoblasts showed increased PCT expression compared to those isolated from healthy placentae. PE sera induced an upregulation of PCT production in macrophages and placental cells. The treatment of PBDM with PE sera in the presence of anti-TNF-α completely abrogated the effect induced by pathologic sera.

CONCLUSION: Trophoblast cells are the main producer of PCT in PE placentae. TNF-α, in association with other circulating factors present in PE sera, upregulates PCT production in macrophages and normal placental cells, thus contributing to the observed increased in circulating PCT in PE sera.

VL - 79 IS - 4 U1 - http://www.ncbi.nlm.nih.gov/pubmed/29427369?dopt=Abstract ER - TY - JOUR T1 - Complement Protein C1q Binds to Hyaluronic Acid in the Malignant Pleural Mesothelioma Microenvironment and Promotes Tumor Growth. JF - Front Immunol Y1 - 2017 A1 - Agostinis, Chiara A1 - Vidergar, Romana A1 - Belmonte, Beatrice A1 - Mangogna, Alessandro A1 - Amadio, Leonardo A1 - Geri, Pietro A1 - Borelli, Violetta A1 - Zanconati, Fabrizio A1 - Tedesco, Francesco A1 - Confalonieri, Marco A1 - Tripodo, Claudio A1 - Kishore, Uday A1 - Bulla, Roberta AB -

C1q is the first recognition subcomponent of the complement classical pathway, which acts toward the clearance of pathogens and apoptotic cells. C1q is also known to modulate a range of functions of immune and non-immune cells, and has been shown to be involved in placental development and sensorial synaptic pruning. We have recently shown that C1q can promote tumor by encouraging their adhesion, migration, and proliferation in addition to angiogenesis and metastasis. In this study, we have examined the role of human C1q in the microenvironment of malignant pleural mesothelioma (MPM), a rare form of cancer commonly associated with exposure to asbestos. We found that C1q was highly expressed in all MPM histotypes, particularly in epithelioid rather than in sarcomatoid histotype. C1q avidly bound high and low molecular weight hyaluronic acid (HA) its globular domain. C1q bound to HA was able to induce adhesion and proliferation of mesothelioma cells (MES) enhancement of ERK1/2, SAPK/JNK, and p38 phosphorylation; however, it did not activate the complement cascade. Consistent with the modular organization of the globular domain, we demonstrated that C1q may bind to HA through ghA module, whereas it may interact with human MES through the ghC. In conclusion, C1q highly expressed in MPM binds to HA and enhances the tumor growth promoting cell adhesion and proliferation. These data can help develop novel diagnostic markers and molecular targets for MPM.

VL - 8 U1 - http://www.ncbi.nlm.nih.gov/pubmed/29209316?dopt=Abstract ER -