Vatairea guianensis lectin stimulates changes in gene expression and release of TNF-α from rat peritoneal macrophages via glycoconjugate binding.
Gabriela Fernandes Oliveira MarquesAlana Freitas PiresVinicius Jose Silva OsterneVanir Reis Pinto-JuniorIvanice Bezerra SilvaMaria Gleiciane Queiroz MartinsMessias Vital OliveiraAngelica Maciel GomesLuiz Augusto Gomes de SouzaMauro Sérgio Gonçalves PavãoBenildo Sousa CavadaAna Maria Sampaio AssreuyKyria Santiago NascimentoPublished in: Journal of molecular recognition : JMR (2021)
Using a rat model of peritonitis, we herein report the inflammatory effect induced by the lectin isolated from Vatairea guianensis (VGL) seeds in the context of interactions between VGL and both toll-like receptor 4 (TLR4) and tumor necrosis factor receptor 1 (TNFR1). Peritoneal macrophages were stimulated with VGL for dose-dependent gene expression and release of TNF-α. In vivo results showed that VGL (1 mg/kg; intraperitoneal) induced peritonitis in female Wistar rats. Leukocyte migration, macrophage activation, and protein leakage were measured 3 and 6 hours after induction. In vitro, peritoneal macrophages were stimulated with VGL for gene expression and TNF-α dosage (mean ± SEM (n = 6), analysis of variance, and Bonferroni's test (P < .05)). In silico, VGL structure was applied in molecular docking with representative glycans. It was found that (a) VGL increases vascular permeability and stimulates leukocyte migration, both rolling and adhesion; (b) lectin-induced neutrophil migration occurs via macrophage stimulation, both in vitro and in vivo; (c) lectin interacts with TLR4 and TNFR1; and (d) stimulates TNF-α gene expression (RT-PCR) and release from peritoneal macrophages. Thus, upon lectin-glycan binding on the cell surface, our results suggest that VGL induces an acute inflammatory response, in turn activating the release of peritoneal macrophages via TNF-α and TLR and/or TNFR receptor pathways.
Keyphrases
- gene expression
- toll like receptor
- inflammatory response
- rheumatoid arthritis
- molecular docking
- cell surface
- dna methylation
- nuclear factor
- immune response
- lipopolysaccharide induced
- lps induced
- binding protein
- high glucose
- oxidative stress
- diabetic rats
- drug induced
- adipose tissue
- low density lipoprotein
- molecular dynamics simulations
- liver failure
- endothelial cells
- acute respiratory distress syndrome
- small molecule
- pseudomonas aeruginosa
- respiratory failure
- cystic fibrosis
- staphylococcus aureus
- cell migration
- candida albicans