Università della Svizzera italiana

Modulation of chemokine responses : synergy and cooperativity

Proudfoot, Amanda E.I. ; Uguccioni, Mariagrazia

In: Frontiers in immunology, 2016, vol. 7, p. 183

Chemokine biology is mediated by more complex interactions than simple monomolecular ligand–receptor interactions, as chemokines can form higher order quaternary structures, which can also be formed after binding to glycosaminoglycans (GAGs) on endothelial cells, and their receptors are found as dimers and/or oligomers at the cell surface. Due to the complexity of the chemokine binding and...

Università della Svizzera italiana

Potential of PEGylated toll-like receptor 7 ligands for controlling inflammation and functional changes in mouse models of asthma and silicosis

Teixeira Ferreira, Tatiana Paula ; Lacerda Mariano, Lívia ; Ghilosso-Bortolini, Roberta ; Santos de Arantes, Ana Carolina ; Fernandes, Andrey Junior ; Berni, Michelle ; Cecchinato, Valentina ; Uguccioni, Mariagrazia ; Maj, Roberto ; Barberis, Alcide ; Machado Rodrigues Silva, Patricia ; Martins, Marco Aurélio

In: Frontiers in immunology, 2016, vol. 7, p. 95

Prior investigations show that signaling activation through pattern recognition receptors can directly impact a number of inflammatory lung diseases. While toll-like receptor (TLR) 7 agonists have raised interest for their ability to inhibit allergen-induced pathological changes in experimental asthma conditions, the putative benefit of this treatment is limited by adverse effects. Our aim...

Università della Svizzera italiana

Chemokine heterocomplexes and cancer : A novel chapter to be written in tumor immunity

D'Agostino, Gianluca ; Cecchinato, Valentina ; Uguccioni, Mariagrazia

In: Frontiers in immunology, 2018, vol. 9, p. 2185

Infiltrating immune cells are a key component of the tumor microenvironment and play central roles in dictating tumor fate, either promoting anti-tumor immune responses, or sustaining tumor growth, angiogenesis and metastasis. A distinctive microenvironment is often associated to different tumor types, with substantial differences in prognosis. The production of a variety of chemotactic...

Università della Svizzera italiana

Redox-mediated mechanisms fuel monocyte responses to CXCL12/HMGB1 in active rheumatoid arthritis

Cecchinato, Valentina ; D'Agostino, Gianluca ; Raeli, Lorenzo ; Nerviani, Alessandra ; Schiraldi, Milena ; Danelon, Gabriela ; Manzo, Antonio ; Thelen, Marcus ; Ciurea, Adrian ; Bianchi, Marco E. ; Rubartelli, Anna ; Pitzalis, Costantino ; Uguccioni, Mariagrazia

In: Frontiers in immunology, 2018, vol. 9, p. 2118

Chemokine synergy-inducing molecules are emerging as regulating factors in cell migration. The alarmin HMGB1, in its reduced form, can complex with CXCL12 enhancing its activity on monocytes via the chemokine receptor CXCR4, while the form containing a disulfide bond, by binding to TLR2 or TLR4, initiates a cascade of events leading to production of cytokines and chemokines. So far, the...

Università della Svizzera italiana

Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release

Venereau, Emilie ; Casalgrandi, Maura ; Schiraldi, Milena ; Antoine, Daniel J. ; Cattaneo, Angela ; De Marchis, Francesco ; Liu, Jaron ; Antonelli, Antonella ; Preti, Alessandro ; Raeli, Lorenzo ; Samadi Shams, Sara ; Yang, Huan ; Varani, Luca ; Andersson, Ulf ; Tracey, Kevin J. ; Bachi, Angela ; Uguccioni, Mariagrazia ; Bianchi, Marco E.

In: The journal of experimental medicine, 2012, vol. 209, no. 9, p. 1519-1528

Tissue damage causes inflammation, by recruiting leukocytes and activating them to release proinflammatory mediators. We show that high-mobility group box 1 protein (HMGB1) orchestrates both processes by switching among mutually exclusive redox states. Reduced cysteines make HMGB1 a chemoattractant, whereas a disulfide bond makes it a proinflammatory cytokine and further cysteine oxidation to...

Università della Svizzera italiana

HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4

Schiraldi, Milena ; Raucci, Angela ; Martínez Muñoz, Laura ; Livoti, Elsa ; Celona, Barbara ; Venereau, Emilie ; Apuzzo, Tiziana ; De Marchis, Francesco ; Pedotti, Mattia ; Bachi, Angela ; Thelen, Marcus ; Varani, Luca ; Mellado, Mario ; Proudfoot, Amanda ; Bianchi, Marco Emilio ; Uguccioni, Mariagrazia

In: The journal of experimental medicine, 2012, vol. 209, no. 3, p. 551-563

After tissue damage, inflammatory cells infiltrate the tissue and release proinflammatory cytokines. HMGB1 (high mobility group box 1), a nuclear protein released by necrotic and severely stressed cells, promotes cytokine release via its interaction with the TLR4 (Toll-like receptor 4) receptor and cell migration via an unknown mechanism. We show that HMGB1- induced recruitment of inflammatory...