EAE;
thymulin;
PBCA nanoparticles;
signalling;
IL-17A;
interferon-gamma;
site-specific phosphorylation of a RelA;
p65;
THYMIC PEPTIDE THYMULIN;
INFLAMMATORY RESPONSE;
DISEASE;
CELLS;
D O I:
10.3390/ijms20215374
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Relapsing-remitting experimental autoimmune encephalomyelitis (rEAE) in mice is a model that closely resembles relapsing-remitting multiple sclerosis in humans. This study aims to investigate a new approach to modulation of the inflammatory response in rEAE mice using a thymic peptide thymulin bound to polybutylcyanoacrylate (PBCA) nanoparticles. PBCA nanoparticles were used to prolong the presence of thymulin in the blood. Cytokine levels in blood were measured by ELISA; NF-kappa B and SAPK/JNK cascade activation, as well as Hsp72 and p53 protein expression, were measured by Western blotting. Animal health statuses were estimated using severity scores. Results showed that the cytokine response in rEAE was multi-staged: an early phase was accompanied by an increase in plasma interferon-gamma, while the interleukin (IL)-17 response was markedly increased at a later stage. The stages were attributed to rEAE induction and maintenance phases. Thymulin significantly alleviated symptoms of rEAE and lowered plasma cytokine levels both in early and later stages of rEAE, and decreased NF-kappa B and SAPK/JNK cascade activation. Thymulin modulated NF-kappaB pathway activity via site-specific phosphorylation of RelA/p65 protein (at Ser276 and Ser536). The effect of nanoparticle-bound thymulin was more pronounced than the effect of free thymulin. Therefore, PBCA-thymulin can be considered a prospective treatment for this pathology.
机构:
Thomas Jefferson Univ, Dept Neurol, 901 Walnut St,Suite 400, Philadelphia, PA 19107 USA
Second Mil Med Univ, Changhai Hosp, Dept Neurol, Shanghai 200433, Peoples R ChinaThomas Jefferson Univ, Dept Neurol, 901 Walnut St,Suite 400, Philadelphia, PA 19107 USA
Xie, Chong
Ciric, Bogoljub
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机构:
Thomas Jefferson Univ, Dept Neurol, 901 Walnut St,Suite 400, Philadelphia, PA 19107 USAThomas Jefferson Univ, Dept Neurol, 901 Walnut St,Suite 400, Philadelphia, PA 19107 USA
Ciric, Bogoljub
Yu, Shuo
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机构:
Thomas Jefferson Univ, Dept Neurol, 901 Walnut St,Suite 400, Philadelphia, PA 19107 USAThomas Jefferson Univ, Dept Neurol, 901 Walnut St,Suite 400, Philadelphia, PA 19107 USA
Yu, Shuo
Zhang, Guang-Xian
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Thomas Jefferson Univ, Dept Neurol, 901 Walnut St,Suite 400, Philadelphia, PA 19107 USAThomas Jefferson Univ, Dept Neurol, 901 Walnut St,Suite 400, Philadelphia, PA 19107 USA
Zhang, Guang-Xian
Rostami, Abdolmohamad
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Thomas Jefferson Univ, Dept Neurol, 901 Walnut St,Suite 400, Philadelphia, PA 19107 USAThomas Jefferson Univ, Dept Neurol, 901 Walnut St,Suite 400, Philadelphia, PA 19107 USA