PMID- 33657463
OWN - NLM
STAT- MEDLINE
DCOM- 20220119
LR  - 20220119
IS  - 1878-3279 (Electronic)
IS  - 0171-2985 (Linking)
VI  - 226
IP  - 3
DP  - 2021 May
TI  - Formyl peptide receptor 2 (FPR2) antagonism is a potential target for the 
      prevention of Brucella abortus 544 infection.
PG  - 152073
LID - S0171-2985(21)00021-8 [pii]
LID - 10.1016/j.imbio.2021.152073 [doi]
AB  - Here, we explore the potential role of formyl peptide receptor 2 (FPR2) during 
      Brucella abortus infection. FPR2 manipulation affected B. abortus internalization 
      but not its growth within macrophages. During the activation of FPR2 induced by 
      its agonist AGP-8694, a high level of Brucella uptake was accompanied by an 
      increase in ERK phosphorylation, while intracellular survival at 24 h 
      postincubation was observed to be associated with slightly reduced nitrite 
      accumulation but augmented superoxide anion production. Attenuated secretion of 
      IL-6 and IL-10 were observed 48 h postincubation in the bone marrow-derived 
      macrophages (BMDMs) treated with the FPR2 antagonist WRW4. An opposite pattern of 
      bacterial uptake was observed upon treatment with the FPR2 antagonist, but no 
      significant changes in the activation of MAPKs or the production of nitrite or 
      superoxide anion were observed. Interestingly, AGP-8694 treatment of mice did not 
      lead to differences in spleen or liver weight but slightly enhanced bacterial 
      proliferation was observed in the spleen. Although the weights of the spleen or 
      liver did not differ, WRW4 treatment led to reduced bacterial proliferation in 
      the spleen. Furthermore, FPR2 antagonist treatment was associated with high serum 
      levels of the proinflammatory cytokines IL-12, TNF-alpha, IFN-gamma and MCP-1, while the 
      production of TNF-alpha was inhibited in AGP-8694-treated mice. IL-6 and IL-10 levels 
      were slightly increased in AGP-8694-treated mice at 24 h postinfection. Our 
      findings demonstrated the contribution of FPR2 via manipulating this receptor 
      using its reported agonist AGP-8694 and antagonist WRW4 in both in vitro and in 
      vivo systems. Although activation of the receptor did not consistently induced 
      Brucella infection, FPR2 inhibition may be a promising strategy to treat 
      brucellosis in animals which encourages further investigation.
CI  - Copyright (c) 2021 Elsevier GmbH. All rights reserved.
FAU - Reyes, Alisha Wehdnesday Bernard
AU  - Reyes AWB
AD  - Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National 
      University, Jinju 52828, Republic of Korea.
FAU - Huy, Tran Xuan Ngoc
AU  - Huy TXN
AD  - Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National 
      University, Jinju 52828, Republic of Korea; Institute of Applied Sciences, Ho Chi 
      Minh City University of Technology - HUTECH, 475A Dien Bien Phu St., Ward 25, 
      Binh Thanh District, Ho Chi Minh City, Viet Nam.
FAU - Vu, Son Hai
AU  - Vu SH
AD  - Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National 
      University, Jinju 52828, Republic of Korea; Institute of Applied Sciences, Ho Chi 
      Minh City University of Technology - HUTECH, 475A Dien Bien Phu St., Ward 25, 
      Binh Thanh District, Ho Chi Minh City, Viet Nam.
FAU - Kang, Chang Keun
AU  - Kang CK
AD  - Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National 
      University, Jinju 52828, Republic of Korea.
FAU - Min, Wongi
AU  - Min W
AD  - Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National 
      University, Jinju 52828, Republic of Korea.
FAU - Lee, Hu Jang
AU  - Lee HJ
AD  - Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National 
      University, Jinju 52828, Republic of Korea.
FAU - Lee, John Hwa
AU  - Lee JH
AD  - College of Veterinary Medicine, Chonbuk National University, Iksan 54596, 
      Republic of Korea.
FAU - Kim, Suk
AU  - Kim S
AD  - Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National 
      University, Jinju 52828, Republic of Korea. Electronic address: kimsuk@gnu.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210223
PL  - Netherlands
TA  - Immunobiology
JT  - Immunobiology
JID - 8002742
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, Formyl Peptide)
RN  - 0 (formyl peptide receptor 2, mouse)
SB  - IM
MH  - Animals
MH  - Anti-Bacterial Agents/*pharmacology
MH  - Biomarkers
MH  - Brucella abortus/*drug effects
MH  - Brucellosis/metabolism/*microbiology/*prevention & control
MH  - Cytokines/biosynthesis
MH  - Disease Management
MH  - Disease Models, Animal
MH  - Disease Susceptibility
MH  - Female
MH  - Host-Pathogen Interactions/*drug effects/immunology
MH  - Macrophages/drug effects/immunology/metabolism/microbiology
MH  - Mice
MH  - *Molecular Targeted Therapy
MH  - RAW 264.7 Cells
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, Formyl Peptide/*antagonists & inhibitors
OTO - NOTNLM
OT  - AGP-8694
OT  - B. abortus
OT  - FPR2
OT  - RAW264.7 cells
OT  - Spleen
OT  - WRW4
EDAT- 2021/03/04 06:00
MHDA- 2022/01/20 06:00
CRDT- 2021/03/03 20:06
PHST- 2020/10/18 00:00 [received]
PHST- 2021/02/16 00:00 [revised]
PHST- 2021/02/18 00:00 [accepted]
PHST- 2021/03/04 06:00 [pubmed]
PHST- 2022/01/20 06:00 [medline]
PHST- 2021/03/03 20:06 [entrez]
AID - S0171-2985(21)00021-8 [pii]
AID - 10.1016/j.imbio.2021.152073 [doi]
PST - ppublish
SO  - Immunobiology. 2021 May;226(3):152073. doi: 10.1016/j.imbio.2021.152073. Epub 
      2021 Feb 23.