PMID- 35320937
OWN - NLM
STAT- MEDLINE
DCOM- 20220502
LR  - 20220502
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - BAFF Blockade Attenuates DSS-Induced Chronic Colitis via Inhibiting NLRP3 
      Inflammasome and NF-kappaB Activation.
PG  - 783254
LID - 10.3389/fimmu.2022.783254 [doi]
LID - 783254
AB  - BACKGROUND: BAFF production is increased in IBD patients. However, the specific 
      role of BAFF in IBD is still uncovered. This study aimed to investigate the 
      expression and function of BAFF in experimental colitis and the potential 
      mechanisms. METHODS: BAFF levels in the serum and colon tissues were measured by 
      ELISA in DSS-induced colitis mice. Mouse-derived BAFF antibody was administered 
      in DSS mice. The changes of body weight, disease activity index (DAI) scores, 
      colon length, spleen weight, histopathological damage, inflammatory indicators, 
      NF-kappaB signaling, and NLRP3 inflammasome were assayed in DSS mice and control. 
      LPS-primed RAW264.7 cells and bone marrow derived macrophages (BMDMs) were 
      treated with BAFF blockage and recombinant mouse BAFF. Inflammatory associated 
      cytokines, NLRP3 inflammasomes and NF-kappaB signaling were detected among groups. 
      RESULTS: BAFF production was elevated systemically and locally in colitis mice. 
      BAFF blockade improved the body weight loss, DAI scores, colon length, spleen 
      weight, and histopathological damage in colitis mice. Immunoflurescence analysis 
      revealed that elevated macrophages in mucosal lamina propria were the primary 
      source of BAFF in the colon. NLRP3 inflammasome and NF-kappaB signaling pathway 
      activation were dramatically inhibited in DSS mice treated with BAFF blockage. In 
      LPS-primed RAW264.7 cells/BMDMs, BAFF blockade decreased the activation of NLRP3 
      inflammasome (NLPR3, ASC, cleaved IL-1beta, cleaved caspase 1) via inhibiting NF-kappaB 
      signaling pathway. Moreover, LPS synergizes with BAFF to promote inflammatory 
      factor secretion and expression of NF-kappaB signaling pathway in RAW264.7 cells. 
      CONCLUSIONS: These results suggested that BAFF blockade protected against colitis 
      partially by relieving inflammation, inhibiting intestinal NLRP3 inflammasome and 
      NF-kappaB signaling pathway from macrophages. BAFF plays an important role in 
      inflammation regulation in IBD, thus providing a novel idea for further research 
      on colitis and experimental evidences for novel potential therapeutic target in 
      IBD.
CI  - Copyright (c) 2022 Zhang, Tao, Chen, Zhao, Feng, Chen and Fu.
FAU - Zhang, Ying
AU  - Zhang Y
AD  - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Tao, Meihui
AU  - Tao M
AD  - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Chen, Chaoyue
AU  - Chen C
AD  - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Zhao, Xi
AU  - Zhao X
AD  - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Feng, Qinyu
AU  - Feng Q
AD  - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Chen, Guang
AU  - Chen G
AD  - Department of Integrated Traditional Chinese and Western Medicine, Tongji 
      Hospital, Tongji Medical College, Huazhong University of Science and Technology, 
      Wuhan, China.
FAU - Fu, Yu
AU  - Fu Y
AD  - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220307
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Inflammasomes)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, mouse)
RN  - 9042-14-2 (Dextran Sulfate)
SB  - IM
MH  - Animals
MH  - *Colitis/chemically induced/drug therapy
MH  - Dextran Sulfate/toxicity
MH  - Humans
MH  - Inflammasomes/metabolism
MH  - Inflammation
MH  - *Inflammatory Bowel Diseases
MH  - Lipopolysaccharides/toxicity
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - Signal Transduction
PMC - PMC8934862
OTO - NOTNLM
OT  - B cell activating factor
OT  - inflammasome
OT  - inflammation
OT  - inflammatory bowel disease
OT  - macrophages
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/03/25 06:00
MHDA- 2022/05/03 06:00
PMCR- 2022/01/01
CRDT- 2022/03/24 05:04
PHST- 2021/09/25 00:00 [received]
PHST- 2022/02/04 00:00 [accepted]
PHST- 2022/03/24 05:04 [entrez]
PHST- 2022/03/25 06:00 [pubmed]
PHST- 2022/05/03 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.783254 [doi]
PST - epublish
SO  - Front Immunol. 2022 Mar 7;13:783254. doi: 10.3389/fimmu.2022.783254. eCollection 
      2022.