Dr. Michela Terlizzi, PhD, is actually a Research Scientist at the Department of Pharmacy of the University of Salerno (Italy). Dr. Terlizzi’s research activity over the years has involved the following lines of research providing an important contribution to the respiratory system physiology field: Study of molecular and cellular pathways involved in the alteration of physiological respiratory function following exposure to carcinogens, cigarette smoke and environmental pollutants both in in vivo models and in human samples; Identification of new inflammatory pathways involved in diseases of the respiratory system.
Abstract
Aims and Objectives:
Sphingosine-1-phosphate (S1P) is a membrane-derived bioactive phospholipid exerting a multitude of effects on respiratory cell physiology and pathology through five S1P receptors (S1PR1-5), although its exact mechanism is still elusive and contradictory.
In our previous studies, we found that S1P induced proliferation of epithelial lung cancer cells through a S1PR3/SPHK II (S1P receptor 3/Sphingosine Kinase II)-dependent intracellular/intranuclear signalling. In this study we aimed to shed light on the role of S1P, whose levels are elevated in lung cancer patients’ plasma, as a modulator of tumor microenvironment, focusing on its effect on circulating cells. Methods :
We used peripheral blood mononuclear cells (PBMCs) isolated by healthy volunteers and lung cancer patients. Cells were stimulated with S1P 10nM and the release of pro-inflammatory cytokines was evaluated after 8 hours from the treatment. Results:
We found that lung cancer-derived PBMCs expressed higher levels of S1PR3 and active ceramidase, compared to healthy cells. Moreover, the administration of S1P induced the release of TNFα, IL-6 and IL-8 from lung cancer- but not from healthy-derived PBMCs in a ceramidase and SPHKs-dependent manner. Interesting, only IL-6 release was S1PR3 dependent. Conclusions:
Our data suggest that S1P regulate the pro-inflammatory signalling in pathological conditions, but not in physiological conditions where S1PR3 is poor expressed and ceramidase enzyme is inactive, implying a protective role of S1P in physiological conditions and highlighting S1P as one of the crucial mediators for lung carcinogenesis-associated inflammatory processes.
COVID-19 and Respiratory System
Chronic Obstructive Pulmonary Disease and Asthma
Lung Cancer
Pneumonia
Cardio Pulmonary Disorders
Idiopathic Pulmonary Fibrosis
Interstitial Lung Disease
Lung Transplantation
Obstructive Sleep Apnea
Occupational Lung Diseases
Pulmonary Hypertension and Pulmonary Rehabilitation