Knocking out Fcgr1 of dorsal root ganglion attenuates the activation of NF-κB/NLRP3 pathway in a rat model of rheumatoid arthritis

Objective To explore the mechanism of peripheral neurons FcγRⅠ regulating pain caused by rheumatoid arthritis. Methods Rheumatoid arthritis models were established in 14 wild-type SD rats and 7 Fcgr1 conditional knockout rats. Wild-type rat control group (control group), rheumatoid arthritis gro...

Full description

Bibliographic Details
Main Author: LIU Fan, SU Si, WANG Tao, YUAN Bo, MA Chao
Format: Article
Language:zho
Published: Institute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College. 2021-07-01
Series:Jichu yixue yu linchuang
Subjects:
Online Access:http://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/a210300.pdf
_version_ 1827390516700905472
author LIU Fan, SU Si, WANG Tao, YUAN Bo, MA Chao
author_facet LIU Fan, SU Si, WANG Tao, YUAN Bo, MA Chao
author_sort LIU Fan, SU Si, WANG Tao, YUAN Bo, MA Chao
collection DOAJ
description Objective To explore the mechanism of peripheral neurons FcγRⅠ regulating pain caused by rheumatoid arthritis. Methods Rheumatoid arthritis models were established in 14 wild-type SD rats and 7 Fcgr1 conditional knockout rats. Wild-type rat control group (control group), rheumatoid arthritis group of wild-type rat (RA group) and rheumatoid arthritis group of Fcgr1 conditional knockout rat (RA+CKO group) were established. Pain behavior was used to detect the changes of mechanical pain threshold and thermal pain threshold 3 and 1 days before modeling and 3, 5, 7 and 9 days after modeling. The expression of Fcgr1 mRNA in dorsal root ganglion (DRG) of Fcgr1 conditional knockout rat was detected by fluorescence in situ hybridization. Immunofluorescence staining was used to detect the changes of IL-1β and IL-18 expression in the DRG and activation of glial cells in the spinal dorsal horn (SDH). Results Compared with the control group, the threshold of mechanical and thermal pain in RA group and (RA+CKO) group were decreased (P<0.05), the mechanical and thermal pain thresholds of the (RA+CKO) group were significantly higher than of RA group(P<0.05). Compared with the RA group, the expression of pNF-κB, NLRP3, IL-1β and IL-18 and the protein level of GFAP and Iba1 in the SDH of (RA+CKO) rats were significantly decreased (P<0.05). Conclusions FcγRⅠ of DRG neurons may promote the synthesis and release of inflammatory cytokines IL-1β and IL-18 through NF-κB/NLRP3 pathway, and cause glial cells activation in the SDH, which may play a role in the mechanism causing pain of rheumatoid arthritis.
first_indexed 2024-03-08T16:53:49Z
format Article
id doaj.art-4b331a98b4e44b0a9e59379987ebfe20
institution Directory Open Access Journal
issn 1001-6325
language zho
last_indexed 2024-03-08T16:53:49Z
publishDate 2021-07-01
publisher Institute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College.
record_format Article
series Jichu yixue yu linchuang
spelling doaj.art-4b331a98b4e44b0a9e59379987ebfe202024-01-05T03:05:36ZzhoInstitute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College.Jichu yixue yu linchuang1001-63252021-07-01417963969Knocking out Fcgr1 of dorsal root ganglion attenuates the activation of NF-κB/NLRP3 pathway in a rat model of rheumatoid arthritisLIU Fan, SU Si, WANG Tao, YUAN Bo, MA Chao0Department of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005, ChinaObjective To explore the mechanism of peripheral neurons FcγRⅠ regulating pain caused by rheumatoid arthritis. Methods Rheumatoid arthritis models were established in 14 wild-type SD rats and 7 Fcgr1 conditional knockout rats. Wild-type rat control group (control group), rheumatoid arthritis group of wild-type rat (RA group) and rheumatoid arthritis group of Fcgr1 conditional knockout rat (RA+CKO group) were established. Pain behavior was used to detect the changes of mechanical pain threshold and thermal pain threshold 3 and 1 days before modeling and 3, 5, 7 and 9 days after modeling. The expression of Fcgr1 mRNA in dorsal root ganglion (DRG) of Fcgr1 conditional knockout rat was detected by fluorescence in situ hybridization. Immunofluorescence staining was used to detect the changes of IL-1β and IL-18 expression in the DRG and activation of glial cells in the spinal dorsal horn (SDH). Results Compared with the control group, the threshold of mechanical and thermal pain in RA group and (RA+CKO) group were decreased (P<0.05), the mechanical and thermal pain thresholds of the (RA+CKO) group were significantly higher than of RA group(P<0.05). Compared with the RA group, the expression of pNF-κB, NLRP3, IL-1β and IL-18 and the protein level of GFAP and Iba1 in the SDH of (RA+CKO) rats were significantly decreased (P<0.05). Conclusions FcγRⅠ of DRG neurons may promote the synthesis and release of inflammatory cytokines IL-1β and IL-18 through NF-κB/NLRP3 pathway, and cause glial cells activation in the SDH, which may play a role in the mechanism causing pain of rheumatoid arthritis.http://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/a210300.pdfrheumatoid arthritis|pain|central sensitization|fc-gamma receptor i (fcγrⅰ)|immune complex
spellingShingle LIU Fan, SU Si, WANG Tao, YUAN Bo, MA Chao
Knocking out Fcgr1 of dorsal root ganglion attenuates the activation of NF-κB/NLRP3 pathway in a rat model of rheumatoid arthritis
Jichu yixue yu linchuang
rheumatoid arthritis|pain|central sensitization|fc-gamma receptor i (fcγrⅰ)|immune complex
title Knocking out Fcgr1 of dorsal root ganglion attenuates the activation of NF-κB/NLRP3 pathway in a rat model of rheumatoid arthritis
title_full Knocking out Fcgr1 of dorsal root ganglion attenuates the activation of NF-κB/NLRP3 pathway in a rat model of rheumatoid arthritis
title_fullStr Knocking out Fcgr1 of dorsal root ganglion attenuates the activation of NF-κB/NLRP3 pathway in a rat model of rheumatoid arthritis
title_full_unstemmed Knocking out Fcgr1 of dorsal root ganglion attenuates the activation of NF-κB/NLRP3 pathway in a rat model of rheumatoid arthritis
title_short Knocking out Fcgr1 of dorsal root ganglion attenuates the activation of NF-κB/NLRP3 pathway in a rat model of rheumatoid arthritis
title_sort knocking out fcgr1 of dorsal root ganglion attenuates the activation of nf κb nlrp3 pathway in a rat model of rheumatoid arthritis
topic rheumatoid arthritis|pain|central sensitization|fc-gamma receptor i (fcγrⅰ)|immune complex
url http://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/a210300.pdf
work_keys_str_mv AT liufansusiwangtaoyuanbomachao knockingoutfcgr1ofdorsalrootganglionattenuatestheactivationofnfkbnlrp3pathwayinaratmodelofrheumatoidarthritis