Mechanisms of action of the galectin-1 and -3 proteins in the allergic inflammation: Study in in vivo and in vitro experimental models and in allergic patients

• Grant number: 15/09858-3
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2015
• End date: November 30, 2017
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Cristiane Damas Gil
• Grantee: Cristiane Damas Gil
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Galectins-1 and -3 (Gal-1 e Gal-3), 14.5 and 29 kDa proteins, respectively, operate as potent endogenous mediators of inflammation by controlling leukocyte transmigration process, release of cytokines and mast cell degranulation, thus contributing to homeostasis of the inflammatory reaction. However, the molecular mechanisms by which these lectins modulate cellular responses, particularly in allergy, are not yet determined. Allergic conjunctivitis is an immune complex disease involving an inflammatory response and consequent ocular disorders that may lead to decreased visual acuity and blindness. Atopy and the continuous rubbing of the eyes which are associated with various clinical conditions such as vernal and atopic keratoconjunctivitis are factors that also contribute to the pathogenesis of other ocular disease, the keratoconus. This pathology is characterized by an asymmetric and progressive corneal ectasia, usually bilateral, causing astigmatism, structural aberrations of the cornea and consequent reduction in vision that can lead to corneal transplantation. Besides the ocular diseases, atopic dermatitis or atopic eczema is the most common chronic skin inflammation of multifactorial etiology, characterized by the production of IgE and Th2 cytokine profile (IL-4 and IL-13). In the treatment of inflammatory diseases, in general, glucocorticoids and immunosuppressive drugs are administered but their adverse effects stimulate search for new therapeutic strategies. Thereby, we will evaluate the expression and mechanism of action of the Gal-1 and Gal-3 proteins in in vivo experimental models of allergic conjunctivitis and atopic dermatitis performed in rodents; in vitro model with human keratocytes and crosslink and; in patients with keratoconus and allergic conjunctivitis. For this purpose, different methodologies will be employed, such as histopathology, immunohistochemistry, enzyme-linked immunosorbent assay (Elisa), western blotting, real time PCR, etc, which will enable detailed understanding of the bioactivity of the proteins and their possible therapeutic applications. (AU)

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)

CORREA, MAB PEREIRA; COSTA ANDRADE, FRANS EBERTH; GIMENES, ALEXANDRE DANTAS; GIL, CRISTIANE DAMAS. Anti-inflammatory effect of galectin-1 in a murine model of atopic dermatitis. JOURNAL OF MOLECULAR MEDICINE-JMM, v. 95, n. 9, p. 1005-1015, SEP 2017. (15/09858-3)

CARLOS, CARLA P.; SILVA, ANALICE A.; GIL, CRISTIANE D.; OLIANI, SONIA M.. Pharmacological treatment with galectin-1 protects against renal ischaemia-reperfusion injury. SCIENTIFIC REPORTS, v. 8, JUN 22 2018. (16/02012-4, 15/09858-3, 11/22113-6)

MELLO-BOSNIC, CLAUDIA; GIMENES, ALEXANDRE DANTAS; OLIANI, SONIA MARIA; GIL, CRISTIANE DAMAS. Treatment with galectin-1 eye drops regulates mast cell degranulation and attenuates the severity of conjunctivitis. European Journal of Pharmacology, v. 833, p. 124-130, AUG 15 2018. (16/02012-4, 15/09858-3)

COSTA ANDRADE, FRANS EBERTH; COVRE, JOYCE LUCIANA; RAMOS, LISANDRA; HAZARBASSANOV, ROSSEN MIHAYLOV; DOS SANTOS, MYRNA SERAPIAO; CAMPOS, MAURO; PEREIRA GOMES, JOSE ALVARO; GIL, CRISTIANE DAMAS. Evaluation of galectin-1 and galectin-3 as prospective biomarkers in keratoconus. BRITISH JOURNAL OF OPHTHALMOLOGY, v. 102, n. 5, p. 700-707, MAY 2018. (15/09858-3)