CIGARRETE SMOKE EFFECTS IN INFLAMATORY RESPONSE OF THE CENTRAL NERVOUS SYSTEM

• Grant number: 12/12921-0
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2012
• End date: September 30, 2014
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Tania Marcourakis
• Grantee: Tania Marcourakis
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Smoking is the major cause of chronic diseases, leading to exacerbate hypertension, chronic obstructive pulmonary disease (COPD), coronary heart disease and others. It is expected that 1.6 billion of people will be smokers in 2030. In 1999, these data led to the creation of policies for tobacco control to avoid contamination of nonsmokers by environmental tobacco smoke (ETS), since the passive smoke is associated with allergic reactions, acute myocardial infarction and lung cancer. The human organism is conditioned to protect against tissue injuries, bacteria and viruses by the Immune System, where the first line of attack is the innate immune response, characterized by fast response and withour specificity. The central nervous system (CNS), a site immune privileged considered due to the presence of the Blood Brain Barrier and the low drain to the lymph nodes of antigen. In this context, the expression of PRRs (Pattern Recognition Receptors) is of the paramount importance, they are able to recognize pathogen associated to molecular patterns (PAMPs) or molecular patterns associated with danger (DAMPs). The binding of PRRs, such as the TLR-4 (Toll-like receptor 4) with its agonist LPS, results in the initiation of an intracellular cascade that culminates in the activation of nuclear factor kB (NF-kB). NF-kB is responsible for mediating the inflammatory response through the transcription of pro-inflammatory cytokines such as IL-1, IL-6, IL-12, TNF-a and anti-inflammatory as IL-10. Characterized by an inflammatory process, COPD is commonly found in chronic smokers and, in addition to pro-inflammatory cytokines IL-1, TNF-a and IL-6, it is possible to detect immunological changes caused by cigarette smoke, such as increased inflammatory cells, mainly monocytes and macrophages. Although well described in the lungs, little is known about the action of cigarette smoke in the CNS. Previous studies from our laboratory have shown that smoke induces changes in antioxidant enzyme and lipid peroxidation in mice. Therefore, this study aims to clarify the effects on inflammatory response induced by LPS and exposure to ETS for 15 consecutive days in C57/BL6 mice. It will be evaluated the pro- and anti-inflammatory cytokines (IL-6, IL-1b, IL-10, TNF-a); the membrane receptor TLR2 and TLR4; iNOS and nuclear factor kB protein expression. (AU)