PMID- 33580557
OWN - NLM
STAT- MEDLINE
DCOM- 20220124
LR  - 20220124
IS  - 1600-0897 (Electronic)
IS  - 1046-7408 (Linking)
VI  - 86
IP  - 1
DP  - 2021 Jul
TI  - Receptor-interacting protein kinase 2 contributes to host innate immune responses 
      against Fusobacterium nucleatum in macrophages and decidual stromal cells.
PG  - e13403
LID - 10.1111/aji.13403 [doi]
AB  - PROBLEM: Chorioamnionitis is caused by a bacterial infection that ascends from 
      the vagina and can cause adverse pregnancy outcomes (APOs). Fusobacterium 
      nucleatum (F. nucleatum) is a periodontal pathogen associated with the occurrence 
      of APOs. In this study, we evaluated whether receptor-interacting protein kinase 
      2 (Ripk2), an adaptor protein of the cytosolic receptors nucleotide-binding 
      oligomerization domain (NOD)1 and NOD2, in macrophages and human decidual stromal 
      cells (hDSCs) contributes to immune responses against F. nucleatum. METHOD OF 
      STUDY: Bone marrow-derived macrophages (BMDMs) isolated from wild-type (WT) and 
      Ripk2-deficient mice and hDSCs were cultured with F. nucleatum (MOI 1, 10, 100). 
      BMDMs and hDSCs were assessed using enzyme-linked immunosorbent assay, Western 
      blot analysis, real-time PCR, and nitrite assay. RESULTS: Fusobacterium 
      nucleatum-induced production of IL-6, but not of TNF-alpha and IL-10, was lower in 
      Ripk2-deficient BMDMs than in WT cells. Western blotting revealed a decrease in 
      F. nucleatum-induced p65 phosphorylation in Ripk2-deficient macrophages, whereas 
      mitogen-activated protein kinases activation was comparable between WT and 
      Ripk2-deficient cells. The production of nitric oxide (NO) in response to F. 
      nucleatum and the gene and protein expression of inducible NO synthase was 
      impaired in Ripk2-deficient BMDMs. In hDSCs, F. nucleatum upregulated the gene 
      and protein expression of NOD1, NOD2, and Ripk2 in a time-dependent manner. F. 
      nucleatum also increased the production of IL-6, CXCL8, and CCL2, whereas this 
      production was decreased by the Ripk2 inhibitors SB203580 and PP2. CONCLUSIONS: 
      In conclusion, Ripk2 signaling appears to contribute to the F. nucleatum-induced 
      immune response and can be a preventive and therapeutic target against APOs.
CI  - (c) 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Park, Ji-Yeon
AU  - Park JY
AD  - Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National 
      University, Gwangju, Republic of Korea.
FAU - Lee, Tae-Sung
AU  - Lee TS
AD  - Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National 
      University, Gwangju, Republic of Korea.
FAU - Noh, Eui Jeong
AU  - Noh EJ
AD  - Department of Obstetrics and Gynecology, College of Medicine, Konyang University, 
      Daejeon, Republic of Korea.
FAU - Jang, Ah-Ra
AU  - Jang AR
AD  - Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National 
      University, Gwangju, Republic of Korea.
FAU - Ahn, Jae-Hun
AU  - Ahn JH
AD  - Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National 
      University, Gwangju, Republic of Korea.
FAU - Kim, Dong-Yeon
AU  - Kim DY
AD  - Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National 
      University, Gwangju, Republic of Korea.
FAU - Jung, Do-Hyeon
AU  - Jung DH
AD  - Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National 
      University, Gwangju, Republic of Korea.
FAU - Song, Eun-Jung
AU  - Song EJ
AUID- ORCID: 0000-0002-1495-488X
AD  - Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National 
      University, Gwangju, Republic of Korea.
FAU - Lee, Yeon-Ji
AU  - Lee YJ
AD  - Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National 
      University, Gwangju, Republic of Korea.
FAU - Lee, Yun-Ji
AU  - Lee YJ
AD  - Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National 
      University, Gwangju, Republic of Korea.
FAU - Lee, Sung Ki
AU  - Lee SK
AUID- ORCID: 0000-0002-6941-192X
AD  - Department of Obstetrics and Gynecology, College of Medicine, Konyang University, 
      Daejeon, Republic of Korea.
FAU - Park, Jong-Hwan
AU  - Park JH
AD  - Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National 
      University, Gwangju, Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210324
PL  - Denmark
TA  - Am J Reprod Immunol
JT  - American journal of reproductive immunology (New York, N.Y. : 1989)
JID - 8912860
RN  - 0 (Toll-Like Receptor 4)
RN  - EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinase 2)
RN  - EC 2.7.11.1 (Ripk2 protein, mouse)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Decidua/*pathology
MH  - Female
MH  - Fusobacterium Infections/*immunology
MH  - Fusobacterium nucleatum/*physiology
MH  - Host-Pathogen Interactions
MH  - Immunity, Innate
MH  - Macrophages/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Receptor-Interacting Protein Serine-Threonine Kinase 2/genetics/*metabolism
MH  - Stromal Cells/*immunology
MH  - Toll-Like Receptor 4/genetics/*metabolism
OTO - NOTNLM
OT  - Fusobacterium nucleatum
OT  - Ripk2
OT  - decidual stromal cells
OT  - macrophages
EDAT- 2021/02/14 06:00
MHDA- 2022/01/27 06:00
CRDT- 2021/02/13 05:55
PHST- 2021/02/08 00:00 [revised]
PHST- 2020/10/15 00:00 [received]
PHST- 2021/02/09 00:00 [accepted]
PHST- 2021/02/14 06:00 [pubmed]
PHST- 2022/01/27 06:00 [medline]
PHST- 2021/02/13 05:55 [entrez]
AID - 10.1111/aji.13403 [doi]
PST - ppublish
SO  - Am J Reprod Immunol. 2021 Jul;86(1):e13403. doi: 10.1111/aji.13403. Epub 2021 Mar 
      24.