A5012779801- Immune Response and Inflammation
- Chemokine receptors and signaling
- Advanced Glycation End Products research
- Inflammatory mediators and NSAID effects
- Asthma and respiratory diseases
- Immunotherapy and Immune Responses
- Cystic Fibrosis Research Advances
- Computational Drug Discovery Methods
- Pneumonia and Respiratory Infections
IRCCS Ospedale San Raffaele
2020-2024
Vita-Salute San Raffaele University
2022
Abstract Chemokine heterodimers activate or dampen their cognate receptors during inflammation. The CXCL12 chemokine forms with the fully reduced (fr) alarmin HMGB1 a physiologically relevant heterocomplex (frHMGB1•CXCL12) that synergically promotes inflammatory response elicited by G-protein coupled receptor CXCR4. molecular details of complex formation were still elusive. Here we show an integrated structural approach frHMGB1•CXCL12 is fuzzy heterocomplex. Unlike previous assumptions,...
High-mobility group box 1 protein (HMGB1) is an ubiquitous nuclear that once released in the extracellular space acts as a Damage Associated Molecular Pattern and promotes inflammation. HMGB1 significantly elevated during Pseudomonas aeruginosa infections has clinical relevance respiratory diseases such Cystic Fibrosis (CF). Salicylates are inhibitors. To address pharmacological inhibition of with small molecules, we explored therapeutic potential pamoic acid (PAM), salicylate limited...
HMGB1 is a key molecule that both triggers and sustains inflammation following infection or injury, involved in large number of pathologies, including cancer. participates the recruitment inflammatory cells, forming heterocomplex with chemokine CXCL12 (HMGB1·CXCL12), thereby activating G-protein coupled receptor CXCR4. Thus, identification molecules disrupt this can offer novel pharmacological opportunities to treat inflammation-related diseases. To identify new HMGB1·CXCL12 inhibitors we...
Abstract Chemokines engage in heterodimeric interactions to activate or dampen their cognate receptors inflammatory conditions. The chemokine CXCL12 forms with the alarmin HMGB1 a patho-physiologically relevant heterocomplex (HMGB1●CXCL12), whose formation synergically promotes response elicited by G-protein coupled receptor CXCR4. However, molecular details of complex were still elusive. Through an integrative structural approach (NMR, AUC, ITC, MST, SAXS) we show that HMGB1●CXCL12...
Abstract HMGB1 is a key molecule that both triggers and sustains inflammation following infection or injury, involved in large number of pathologies, including cancer. participates to the recruitment inflammatory cells forming heterocomplex with chemokine CXCL12 (HMGB1•CXCL12), herewith activating G-protein coupled receptor CXCR4. Thus, identification molecules disrupt this can offer novel pharmacological opportunities treat related diseases. To identify new HMGB1•CXCL12 inhibitors we have...
Abstract Background. High-mobility group box 1 protein (HMGB1) is an ubiquitous nuclear that once released in the extracellular space acts as a Damage Associated Molecular Pattern and promotes inflammation. HMGB1 significantly elevated during Pseudomonas aeruginosa infections has clinical relevance respiratory diseases such Cystic Fibrosis (CF). Salicylates are inhibitors. To address pharmacological inhibition of with small molecules, we explored therapeutic potential pamoic acid (PAM),...