PMID- 35444446
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 1178-7031 (Print)
IS  - 1178-7031 (Electronic)
IS  - 1178-7031 (Linking)
VI  - 15
DP  - 2022
TI  - Pulsed-Ultrasound Irradiation Induces the Production of Itaconate and Attenuates 
      Inflammatory Responses in Macrophages.
PG  - 2387-2395
LID - 10.2147/JIR.S361609 [doi]
AB  - BACKGROUND: Itaconate is a key metabolite in the innate immune system and exerts 
      strong anti-inflammatory effects in macrophages. For the production of itaconate 
      in macrophages, immune-responsive gene 1 (IRG1) is an imperative enzyme, and 
      activating the IRG1-itaconate pathway is reported to alleviate inflammatory 
      diseases by upregulating nuclear factor-erythroid 2-related factor 2 (NRF2). 
      However, there are very few reports on strategies to increase itaconate 
      production. Ultrasound therapy is a widely used intervention for 
      anti-inflammatory and soft-tissue regeneration purposes. Here we show the effect 
      of ultrasound irradiation on the production of itaconate in macrophages. METHODS: 
      Murine bone marrow-derived macrophages (BMDMs) were exposed to pulsed ultrasound 
      (3.0 W/cm(2)) for 5 minutes. Three hours after irradiation, the intracellular 
      levels of metabolites and mRNA expression levels of Irg1 and Nrf2 were measured 
      using CE/MS and qPCR, respectively. To evaluate macrophage inflammation status, 3 
      h after irradiation, the cells were stimulated with 100 ng/mL lipopolysaccharide 
      (LPS) for 1.5 h and the mRNA expression levels of pro-inflammatory factors 
      (Il-1beta, Il-6, and Tnf-alpha) were measured. Student's t-test, one-way ANOVA and 
      Tukey's multiple comparison test were used for statistical processing, and the 
      significance level was set to less than 5%. RESULTS: Ultrasound irradiation 
      significantly increased the intracellular itaconate level and the expression 
      levels of Irg1 and Nrf2 in BMDMs. Upregulation of Il-1beta, Il-6, and Tnf-alpha by LPS 
      was significantly suppressed in BMDMs treated with ultrasound. Ultrasound 
      irradiation did not affect cell viability and apoptosis. CONCLUSION: Ultrasound 
      irradiation induces the production of itaconate by upregulating Irg1 expression 
      and attenuates inflammatory responses in macrophages via Nrf2. These results 
      suggest that ultrasound is a potentially useful method to increase itaconate 
      production in macrophages.
CI  - (c) 2022 Yamaguchi et al.
FAU - Yamaguchi, Atomu
AU  - Yamaguchi A
AD  - Department of Rehabilitation Science, Kobe University Graduate School of Health 
      Sciences, Kobe, Japan.
FAU - Maeshige, Noriaki
AU  - Maeshige N
AUID- ORCID: 0000-0002-3573-347X
AD  - Department of Rehabilitation Science, Kobe University Graduate School of Health 
      Sciences, Kobe, Japan.
FAU - Ma, Xiaoqi
AU  - Ma X
AD  - Department of Rehabilitation Science, Kobe University Graduate School of Health 
      Sciences, Kobe, Japan.
FAU - Uemura, Mikiko
AU  - Uemura M
AUID- ORCID: 0000-0001-8461-7355
AD  - Department of Rehabilitation Science, Kobe University Graduate School of Health 
      Sciences, Kobe, Japan.
FAU - Noguchi, Hikari
AU  - Noguchi H
AD  - Department of Rehabilitation Science, Kobe University Graduate School of Health 
      Sciences, Kobe, Japan.
FAU - Matsuda, Mami
AU  - Matsuda M
AD  - Graduate School of Science, Technology and Innovation, Kobe University, Kobe, 
      Japan.
FAU - Nishimura, Yuya
AU  - Nishimura Y
AD  - Graduate School of Science, Technology and Innovation, Kobe University, Kobe, 
      Japan.
FAU - Hasunuma, Tomohisa
AU  - Hasunuma T
AUID- ORCID: 0000-0002-8382-2362
AD  - Graduate School of Science, Technology and Innovation, Kobe University, Kobe, 
      Japan.
AD  - Engineering Biology Research Center, Kobe University, Kobe, Japan.
FAU - Kondo, Hiroyo
AU  - Kondo H
AD  - Department of Food Science and Nutrition, Nagoya Women's University, Nagoya, 
      Japan.
FAU - Fujino, Hidemi
AU  - Fujino H
AUID- ORCID: 0000-0002-6304-0654
AD  - Department of Rehabilitation Science, Kobe University Graduate School of Health 
      Sciences, Kobe, Japan.
LA  - eng
PT  - Journal Article
DEP - 20220413
PL  - New Zealand
TA  - J Inflamm Res
JT  - Journal of inflammation research
JID - 101512684
PMC - PMC9013924
OTO - NOTNLM
OT  - IRG1
OT  - NRF2
OT  - inflammation
OT  - itaconate
OT  - macrophage
OT  - pulsed-ultrasound
COIS- The authors declare no competing interests in this work.
EDAT- 2022/04/22 06:00
MHDA- 2022/04/22 06:01
PMCR- 2022/04/13
CRDT- 2022/04/21 05:43
PHST- 2022/02/09 00:00 [received]
PHST- 2022/04/07 00:00 [accepted]
PHST- 2022/04/21 05:43 [entrez]
PHST- 2022/04/22 06:00 [pubmed]
PHST- 2022/04/22 06:01 [medline]
PHST- 2022/04/13 00:00 [pmc-release]
AID - 361609 [pii]
AID - 10.2147/JIR.S361609 [doi]
PST - epublish
SO  - J Inflamm Res. 2022 Apr 13;15:2387-2395. doi: 10.2147/JIR.S361609. eCollection 
      2022.