Evaluation of the mechanisms involved in the MUC5A production from lung epithelial cell line stimulated by histamine

• Grant number: 15/02492-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): July 01, 2015
• Effective date (End): June 30, 2016
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Sandra Helena Penha de Oliveira
• Grantee: Fernanda Manaia Demarqui
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

During an asthmatic reaction the broncoconstriction takes place and combined with the excess of mucus induces a reduced air flow in the airways. Immune and non immune stimulation as well as environmental factors can trigger the development of the allergic inflammation through the activation of resident cells like mast cells that then begin to release several mediators among which can be find molecules of histamine. In the allergic proccess, the histamine liberation takes effects like vasodilation, bronchoconstriction and mucus overproduction. Likewise histamine, other molecules are present in the development of an asthmatic profile of airway inflammation as the citokynes. This citokynes increase the amount of genes that are responsible for production of substances that cause the aggravation of inflammatory simptoms like mucus overproduction. In asthma disease, MUC expression is evidenced and can be induced by a variety of stimulus, whereby citokynes, elastase and EGF, and there are several mechanisms of intracellular signaling that can also be envolved in this proccess. The mechanism in which the mucus production occurs by goblet cells in the epithelium is an important problem that must be better understood for the resolution of allergic inflammation. This way, the present study aims to investigate the mechanims involved in the expression and production of MUC5AC by lung epithelial cells stimulated by histamine. For this purpose lung epithelial cells line (LA4) will be used and stimullated by different concentrations of histamine and the mechanisms envolved in the production of MUC5AC will be analyzed by immunocytochemestry, ELISA, western blot and real time PCR. Thereby, understanding the mechanisms involved in the expression and production of MUC5AC by epithelial cells stimulated by histamine can initiate a new stage in the discovery of pharmacological tools that can be employed in this proccess to reduce asthma symptoms linked to MUC5A production.