EFFECTS OF THE EXPOSURE TO TOBACCO PRODUCTS ON CD4 + T LYMPHOCYTES INVOLVED IN THE GENESIS OF MULTIPLE SCLEROSIS

• Grant number: 20/14368-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: February 01, 2022
• End date: March 31, 2026
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Sandra Helena Poliselli Farsky
• Grantee: Pablo Rhansan dos Santos Scharf
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 22/14025-4 - Effects of heated tobacco vapor, nicotine, and cigarette smoke exposures on C. elegans neuroimmune interactions and host defense, BE.EP.DR

Abstract

Smoking is related to the pathogenesis of multiple sclerosis (MS), a demyelinating neurodegenerative autoimmune disease, mediated by T lymphocytes; However, the participation of tobacco and nicotine combustion components in its genesis is controversial. Non-combustible cigarettes (heat-not-burn tobacco; HNBT) have emerged as less toxic alternatives to conventional cigarettes (CC) for releasing nicotine, propylene glycol, and glycerin, and lower levels of tobacco burning products compared to CC. This project aims to analyze the effects of in vitro and in vivo exposure to HNBT, CC, or nicotine solution on the biology of CD4 + T lymphocytes and the clinical evolution of experimental autoimmune encephalomyelitis (EAE). Therefore, CD4 + T lymphocytes from healthy or MS patients will be collected and exposed in vitro to nicotine, HNBT, or CC to assess the effects on Th1, Th17, and Treg polarization, proliferation, calcium influx, activation of the nuclear factor kappa B ( NFºB), activator protein 1 (AP-1), nuclear factor of activated T cells 1 (NFAT1) and aryl hydrocarbon receptor (AhR) by flow cytometry; secretion of cytokines by ELISA; and the levels of mi-RNAs 21, 145, 155, 233 and 326 by RT-qPCR. C57Bl / 6 mice will be submitted to EAE and will be exposed to the aerosolized nicotine solution, HNBT, or CC during peak disease (14th to 20th after EAE induction) to assess clinical evolution, CNS histopathology, occludent zonula expression, and claudin 1 and 5 by western blotting, frequency of lymphocytes by flow cytometry, of the expressions of NFºB, AP-1, NFAT1, and AhR. It is still an objective to request a BEPE stage to evaluate the effects of exposure to nicotine and nicotinic receptors at the different endpoints observed in the in vitro and in vivo assays in the experimental model of C. elegans at the Neurotoxicity Laboratory of prof. Dr. Michael Aschner of Albert Einstein College of Medicine, New York - USA. Associated, the results obtained will contribute to the elucidation of nicotine and CC combustion products on the development of EAE and elucidate the toxicity of HNBTs on the central nervous system and immune system.

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

HEBEDA, CRISTINA BICHELS; SAVIOLI, ANNA CAROLINA; SCHARF, PABLO; DE PAULA-SILVA, MARINA; GIL, CRISTIANE DAMAS; FARSKY, SANDRA HELENA POLISELLI; SANDRI, SILVANA. Neutrophil depletion in the pre-implantation phase impairs pregnancy index, placenta and fetus development. FRONTIERS IN IMMUNOLOGY, v. 13, p. 12-pg., 2022-09-29. (14/07328-4, 20/14368-3)

SCHARF, PABLO; SANDRI, SILVANA; RIZZETTO, FELIPE; XAVIER, LUANA FILIPPI; GROSSO, DANIELA; CORREIA-SILVA, REBECA D.; FARSKY, PEDRO S.; GIL, CRISTIANE D.; FARSKY, SANDRA HELENA POLISELLI. GPCRs overexpression and impaired fMLP-induced functions in neutrophils from chronic kidney disease patients. FRONTIERS IN IMMUNOLOGY, v. 15, p. 13-pg., 2024-08-26. (20/14368-3, 14/07328-4)

SCHARF, PABLO; SANDRI, SILVANA; BORGES, PAMELA PACASSA; DE OLIVEIRA, TIAGO FRANCO; FARSKY, SANDRA HELENA POLISELLI. A single and short exposure to heated tobacco vapor or cigarette smoke affects macrophage activation and polarization. Toxicology, v. 506, p. 5-pg., 2024-06-14. (20/14368-3, 19/19573-7, 22/11779-8)

SCHARF, PABLO; RIZZETTO, FELIPE; XAVIER, LUANA FILIPPI; POLISELLI FARSKY, SANDRA HELENA. Xenobiotics Delivered by Electronic Nicotine Delivery Systems: Potential Cellular and Molecular Mechanisms on the Pathogenesis of Chronic Kidney Disease. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 18, p. 18-pg., 2022-09-01. (19/19573-7, 20/14368-3)