Ectopic expression of SIGIRR in the colon ameliorates colitis in mice by downregulating TLR4/NF-κB overactivation.
Inflammatory bowel disease (IBD) is characterized by uncontrolled immune responses in inflamed mucosa, especially the TLR (Toll-like receptor) signaling pathway. Single Ig domain containing IL-1 receptor-related molecule (SIGIRR), a negative regulator of the TLR signaling pathway, whether had a therapeutic effect in a mouse model of IBD, and the underlying mechanism has not been investigated.



Coacervation was used to prepare chitosan/pUNO-SIGIRR nanoparticles. The nanoparticles were administered to mice with colitis using enteroclysis. The disease activity index (DAI) and hematoxylin and eosin staining (HE) staining were used to evaluate the therapeutic effects of the SIGIRR nanoparticles. Immunohistochemistry was performed to elucidate the underlying mechanism driving these effects.



Chitosan/pUNO-SIGIRR nanoparticles were successfully constructed and were spherical, with a mean diameter of less than 100nm, and the plasmid encapsulating efficiency was 99.9%. The chitosan/pUNO-SIGIRR nanoparticles attenuated colonic tissue inflammation through the inhibition of TLR4/NF-κB overactivation by downregulating TLR4, MyD88 and NF-κB p65 expression in a mouse model of colitis.



The novel chitosan/pUNO-SIGIRR nanoparticles had a therapeutic effect on IBD in a mouse model through the inhibition of TLR4/NF-κB overactivation.
Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, No. 17,Yongwai Zheng Street, Nanchang, China; Institute of Molecular Medicine, Jiangxi Academy of Medical Sciences, No. 461, Bayi Road, Nanchang, China; Department of Clinical Laboratory, Zhejiang Provincial People's Hospital,158 Shangtang Road, Hangzhou, China.
Jinlin
J
Liu
Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, No. 17,Yongwai Zheng Street, Nanchang, China; Department of Rheumatology, Zhejiang Provincial People's Hospital,158 Shangtang Road, Hangzhou, China.
Yanxia
Y
Chen
Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, No. 17,Yongwai Zheng Street, Nanchang, China.
Dongsheng
D
Liu
Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, No. 17,Yongwai Zheng Street, Nanchang, China.
Wei
W
Liu
Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, No. 17,Yongwai Zheng Street, Nanchang, China.
Sijun
S
Hu
Institute of Molecular Medicine, Jiangxi Academy of Medical Sciences, No. 461, Bayi Road, Nanchang, China. Electronic address: jxznj@tom.com.
Nanjin
N
Zhou
Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, No. 17,Yongwai Zheng Street, Nanchang, China. Electronic address: doctorxieyong@163.com.
Yong
Y
Xie
D000818:Animals; D048271:Chitosan; D003092:Colitis / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D004195:Disease Models, Animal; D000066630:Ectopic Gene Expression; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D053758:Nanoparticles; D017472:Receptors, Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
D048271:Chitosan; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D017472:Receptors, Interleukin-1; D051197:Toll-Like Receptor 4; C484529:SIGIRR protein, mouse
Colitis; Nanoparticles; SIGIRR; TLRs