A mathematical model relates intracellular TLR4 oscillations to sepsis progression

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art_STAN_A_mathematical_model_relates_intracellular_TLR4_oscillations_to_2018.PDF (1.02 MB)
Citações na Scopus
4
Tipo de produção
article
Data de publicação
2018
DOI
Scopus
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
BIOMED CENTRAL LTD.
Autores
STAN, R. C.
CAMARGO, M. M. De
Citação
BMC RESEARCH NOTES, v.11, n.1, article ID 462, p, 2018
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Objective: Oscillations of physiological parameters describe many biological processes and their modulation is determinant for various pathologies. In sepsis, toll-like receptor 4 (TLR4) is a key sensor for signaling the presence of Gram-negative bacteria. Its intracellular trafficking rates shift the equilibrium between the pro- and anti-inflammatory downstream signaling cascades, leading to either the physiological resolution of the bacterial stimulation or to sepsis. This study aimed to evaluate the effects of TLR4 increased expression and intracellular trafficking on the course and outcome of sepsis. Results: Using a set of three differential equations, we defined the TLR4 fluxes between relevant cell organelles. We obtained three different regions in the phase space: (1) a limit-cycle describing unstimulated physiological oscillations, (2) a fixed-point attractor resulting from moderate LPS stimulation that is resolved and (3) a double-attractor resulting from sustained LPS stimulation that leads to sepsis. We used this model to describe available hospital data of sepsis patients and we correctly characterize the clinical outcome of these patients. © 2018 The Author(s).
Palavras-chave
Inflammation, Intracellular trafficking, Ordinary differential equations, Oscillations, Sepsis
URI
https://observatorio.fm.usp.br/handle/OPI/31026
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - LIM/51