PMID- 33559709
OWN - NLM
STAT- MEDLINE
DCOM- 20211018
LR  - 20240226
IS  - 1420-908X (Electronic)
IS  - 1023-3830 (Linking)
VI  - 70
IP  - 3
DP  - 2021 Mar
TI  - Tripterine ameliorates monosodium urate crystal-induced gouty arthritis by 
      altering macrophage polarization via the miR-449a/NLRP3 axis.
PG  - 323-341
LID - 10.1007/s00011-021-01439-0 [doi]
AB  - OBJECTIVE: Tripterine (Trip) is frequently applied to alleviate inflammation in 
      various diseases such as rheumatoid arthritis. Macrophages have both 
      anti-inflammatory and pro-inflammatory functions. However, whether Trip can 
      inhibit cell inflammation in gouty arthritis (GA) remains undiscovered and 
      whether the mechanism involved in macrophage polarization is also undetermined. 
      This paper aims to study the effects of Trip on inflammation and macrophage 
      polarization in GA. METHODS: Monosodium urate (MSU) crystals were used to 
      establish GA mouse models, and bone marrow-derived macrophages (BMDMs) were 
      induced to construct GA cell models. Pretreatments of Trip and injection of 
      Antagomir-449a/Agomir-449a were performed on mice for 6 days. The effects of Trip 
      and miR-449 on toe swelling, joint damage of GA mouse were examined. The 
      alternations on cell morphology, cell proliferation marker Ki67, inflammatory 
      cytokines, NLRP3 inflammasome, and NF-kappaB signaling-related proteins were also 
      determined both in vivo and in vitro. Dual-luciferase reporter gene assay and RIP 
      assay were adopted to estimate the targeting relationship between miR-449a and 
      NLRP3. RESULTS: GA mouse model had increased M1 macrophage, intensified 
      inflammation response, along with suppressed miR-449a expression. Following 
      administration of Trip attenuated cell inflammation, promoted macrophage polarize 
      to M2 phenotype, elevated miR-449a expression, repressed the phosphorylation 
      levels of NF-kappaB signaling-related proteins, and diminished IkappaBalpha expression in 
      vivo and in vitro. However, inhibition of miR-449a hindered the favorable effect 
      of Trip on GA and increased NLRP3 inflammasome expression. MiR-449a directly 
      targeted NLRP3. Overexpression of NLRP3 partially eliminated the biological 
      effects of miR-449a agonist. CONCLUSION: Trip regulates macrophage polarization 
      through miR-449a/NLRP3 axis and the STAT3/NF-kappaB pathway to mitigate GA. The 
      elucidation on the molecular mechanism of Trip in GA may provide theoretical 
      guidance for clinical therapy of GA.
FAU - Wang, Yu
AU  - Wang Y
AUID- ORCID: 0000-0002-3217-131X
AD  - Department of Rheumatism Immunology, First Affiliated Hospital of Harbin Medical 
      University, Harbin, Heilongjiang, 150001, People's Republic of China. 
      wangyu11299@sina.com.
LA  - eng
PT  - Journal Article
PT  - Retracted Publication
DEP - 20210209
PL  - Switzerland
TA  - Inflamm Res
JT  - Inflammation research : official journal of the European Histamine Research 
      Society ... [et al.]
JID - 9508160
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (Inflammasomes)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn449 microRNA, mouse)
RN  - 0 (NF-kappa B)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, mouse)
RN  - 0 (Pentacyclic Triterpenes)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - 268B43MJ25 (Uric Acid)
RN  - L8GG98663L (celastrol)
SB  - IM
RIN - Inflamm Res. 2023 Jan;72(1):3. PMID: 36063187
MH  - Animals
MH  - Ankle Joint/drug effects/immunology/pathology
MH  - Anti-Inflammatory Agents/pharmacology/*therapeutic use
MH  - Arthritis, Gouty/chemically induced/*drug therapy
MH  - Cytokines/genetics/immunology
MH  - HEK293 Cells
MH  - Humans
MH  - Inflammasomes/genetics/immunology
MH  - Macrophages/drug effects/immunology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - *MicroRNAs
MH  - NF-kappa B/immunology
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/genetics/*immunology
MH  - Pentacyclic Triterpenes/pharmacology/*therapeutic use
MH  - Phenotype
MH  - STAT3 Transcription Factor/immunology
MH  - Toe Joint/drug effects/immunology/pathology
MH  - Uric Acid
MH  - Mice
OTO - NOTNLM
OT  - Gouty arthritis
OT  - Macrophage polarization
OT  - MiR-449a
OT  - NLRP3 inflammasome
OT  - Tripterine
EDAT- 2021/02/10 06:00
MHDA- 2021/10/21 06:00
CRDT- 2021/02/09 08:45
PHST- 2020/10/25 00:00 [received]
PHST- 2021/01/28 00:00 [accepted]
PHST- 2021/01/19 00:00 [revised]
PHST- 2021/02/10 06:00 [pubmed]
PHST- 2021/10/21 06:00 [medline]
PHST- 2021/02/09 08:45 [entrez]
AID - 10.1007/s00011-021-01439-0 [pii]
AID - 10.1007/s00011-021-01439-0 [doi]
PST - ppublish
SO  - Inflamm Res. 2021 Mar;70(3):323-341. doi: 10.1007/s00011-021-01439-0. Epub 2021 
      Feb 9.