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Obesity and Type 2 Diabetes mellitus induce lipopolysaccharide tolerance in rat neutrophils.


ABSTRACT: Obesity and diabetes implicate in various health complications and increased mortality caused by infection. Innate immune system is broadly affected by these diseases, leading the patients to an immunosuppressive state. A mechanism that leads innate immune cells to a less capacity of killing microorganism is the impaired TLR4 activation. TLR4 recognizes a component of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS), and when activated increases the production of inflammatory substances. Neutrophils are components of the innate immune system and are the first responders to an invading agent. The correct activation of TLR4 in these cells is required for the initiation of the inflammatory process and elimination of the microorganisms. The aim of this study was to evaluate the influence of type 2 diabetes and obesity in the TLR4 pathway in rat neutrophils. Two experimental models were used: Goto-Kakizaki rats and high-fat-diet induced obese Wistar rats. To evaluate neutrophil response to LPS, intratracheal LPS instillation was used. Neutrophils from obese and diabetic animals exhibited tolerance to LPS, mainly by the impaired production of cytokines and chemokines and the low content of phospho-NF?B and phospho-IKB?. Neutrophils from both experimental models had increased cell death, impaired in vivo migration and myeloperoxidase activity.

SUBMITTER: Kuwabara WMT 

PROVIDER: S-EPMC6277411 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Obesity and Type 2 Diabetes mellitus induce lipopolysaccharide tolerance in rat neutrophils.

Kuwabara Wilson Mitsuo Tatagiba WMT   Yokota Caroline Naomi Fukusawa CNF   Curi Rui R   Alba-Loureiro Tatiana Carolina TC  

Scientific reports 20181203 1


Obesity and diabetes implicate in various health complications and increased mortality caused by infection. Innate immune system is broadly affected by these diseases, leading the patients to an immunosuppressive state. A mechanism that leads innate immune cells to a less capacity of killing microorganism is the impaired TLR4 activation. TLR4 recognizes a component of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS), and when activated increases the production of inflammato  ...[more]

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