Vaccines R&D & Vaccination

Fiorentina Roviezzo, Associate professor in Pharmacology, has completed her PhD by carried out in part at University of Naples Federico II and in part at William Harvey Research Institute London. She completed her Postdoctoral studies from University of Salerno. The main focus of her work is investigating on the regulation mechanisms of inflammatory response.  She focused her attention on an important eNOS signalling pathway that involves sphingolipids and mostly sphingosine-1-phosphate (S1P). S1P is involved in biological functions including cell growth and survival, differentiation, calcium homeostasis and in smooth muscle contraction. Now, she is focused on lung inflammatory diseases such as asthma and COPD. To date, she was involved in research projects regarding the role of S1P in these pathologies and she has demonstrated a key contribute in the control of airway function. This scientific production is also validated by more than 60 papers published on international journals at impact factor known.

Allergen challenge promotes sphingosine-1-phosphate (S1P) signaling in the lung and determines in the mouse a disease closely mimicking the cardinal features of asthma. Here we have investigated the role of TLR-4 in S1P/S1P1 pathway in the lung and its contribution to S1P-induced lung inflammation. BALB/c and TLR-4 defective (C3H/HeJ) mice received subcutaneous administration of S1P (10 ng/mouse), LPS (0.1 µg/mouse) or S1P+LPS at days 0 and 7. A group of BALB/c mice were pre-treated with the purified rabbit anti-TLR-4 (10 µg/mouse). Subcutaneous administration of S1P induced airway hyper-responsiveness and pulmonary inflammation coupled to an increase in the percentage of dendritic cells and macrophages into the lung of BALB/c mice, and a reduction of dendritic cell in the mediastinic lymph node. This effect was potentiated by LPS in S1P-treated BALB/c mice. Conversely, S1P did not affect lung function and pulmonary immune microenvironment in TLR-4 defective mice as well as in mice pre-treated with a purified rabbit anti-TLR-4 antibody. Following subcutaneous S1P administration, TLR-4 up-regulation occurred in the lung of S1P-treated BALB/c mice, implying a cross-talk between S1P and TLR-4, as confirmed by the co-immunoprecipitation of S1P1 and TLR-4 in an S1P-dependent manner. In conclusion, our data suggest a novel receptor cooperation in which the functional interaction between S1P1 and TLR-4 results in an enhanced allergic inflammatory response in the lung, paving the way for the biological role of S1P highly detected in the BAL of asthmatic patients. Allergen challenge promotes sphingosine-1-phosphate (S1P) signaling in the lung and determines in the mouse a disease closely mimicking the cardinal features of asthma. Here we have investigated the role of TLR-4 in S1P/S1P1 pathway in the lung and its contribution to S1P-induced lung inflammation. BALB/c and TLR-4 defective (C3H/HeJ) mice received subcutaneous administration of S1P (10 ng/mouse), LPS (0.1 µg/mouse) or S1P+LPS at days 0 and 7. A group of BALB/c mice were pre-treated with the purified rabbit anti-TLR-4 (10 µg/mouse). Subcutaneous administration of S1P induced airway hyper-responsiveness and pulmonary inflammation coupled to an increase in the percentage of dendritic cells and macrophages into the lung of BALB/c mice, and a reduction of dendritic cell in the mediastinic lymph node. This effect was potentiated by LPS in S1P-treated BALB/c mice. Conversely, S1P did not affect lung function and pulmonary immune microenvironment in TLR-4 defective mice as well as in mice pre-treated with a purified rabbit anti-TLR-4 antibody. Following subcutaneous S1P administration, TLR-4 up-regulation occurred in the lung of S1P-treated BALB/c mice, implying a cross-talk between S1P and TLR-4, as confirmed by the co-immunoprecipitation of S1P1 and TLR-4 in an S1P-dependent manner. In conclusion, our data suggest a novel receptor cooperation in which the functional interaction between S1P1 and TLR-4 results in an enhanced allergic inflammatory response in the lung, paving the way for the biological role of S1P highly detected in the BAL of asthmatic patients.