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Intranuclear delivery of synthetic nuclear factor-kappa B p65 reduces inflammasomes after surgery

 So Yeong Cheon  ;  Jeong Min Kim  ;  Eun Jung Kim  ;  So Yeon Kim  ;  Eun Hee Kam  ;  Chun-Chang Ho  ;  Sang-Kyou Lee  ;  Bon-Nyeo Koo 
 Biochemical Pharmacology, Vol.158 : 141-152, 2018 
Journal Title
 Biochemical Pharmacology 
Issue Date
Abdominal surgery ; Inflammasome ; Nuclear factor kappa B ; Pro-inflammatory marker ; Splenocyte
Patients undergoing surgery can suffer from various complications, including post-operative bleeding, local or systematic infection, and neurologic disorders. Major surgery can initiate innate immune responses and trigger overproduction of inflammatory mediators, which can contribute to organ dysfunction. Inflammasomes are innate immune complexes, which are connected to the pathogenesis of various diseases, including atherosclerosis, hemorrhagic brain injury, and Alzheimer's disease. In the present study, we hypothesized that nucleotide-binding oligomerization domain-containing-like receptor protein (NLRP) inflammasomes may have a role in the pathological effects of surgery. Therefore, we designed a protein inhibitor of nuclear factor kappa B (NF-κB) p65 transcripts, called nt-p65-TMD (nuclear transducible (nt) transcription modulated domain (TMD) of RelA (p65)), that can penetrate the nucleus, and evaluated its therapeutic efficacy for dampening surgery-induced inflammasome activation. It was found that the nt-p65-TMD significantly reduced the NLRP1 inflammasome complex components (NLRP1, ASC, and Caspase-1) and interleukin (IL)-1β and IL-18 productions in the spleen after surgery. In the spleen, specific cell population and selective mediators were altered after surgery with/without nt-p65-TMD treatment. Also, we found that treatment of nt-p65-TMD decreased cell death in the spleen after surgery. Therefore, nt-p65-TMD is a potential novel strategy for reducing surgery-induced NLRP1 inflammasome and complications.
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1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
Yonsei Authors
구본녀(Koo, Bon-Nyeo) ORCID logo https://orcid.org/0000-0002-3189-1673
김소연(Kim, So Yeon) ORCID logo https://orcid.org/0000-0001-5352-157X
김은정(Kim, Eun Jung) ORCID logo https://orcid.org/0000-0002-5693-1336
김정민(Kim, Jeongmin) ORCID logo https://orcid.org/0000-0002-0468-8012
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