PMID- 37782452
OWN - NLM
STAT- MEDLINE
DCOM- 20240201
LR  - 20240315
IS  - 1573-2576 (Electronic)
IS  - 0360-3997 (Linking)
VI  - 47
IP  - 1
DP  - 2024 Feb
TI  - LIF Aggravates Pulpitis by Promoting Inflammatory Response in Macrophages.
PG  - 307-322
LID - 10.1007/s10753-023-01910-6 [doi]
AB  - Leukemia inhibitory factor (LIF) has been recognized as a novel inflammatory 
      modulator in inflammation-associated diseases. This study aimed to investigate 
      the modulation of LIF in dental pulp inflammation. Experimental pulpitis was 
      established in wild-type (WT) and Lif-deficient (Lif(-/-)) mice. Histological and 
      immunostaining analyses were conducted to assess the role of LIF in the 
      progression of pulpitis. Mouse macrophage cell line (RAW264.7) was treated with 
      LPS to simulate an inflammatory environment. Exogenous LIF was added to this 
      system to examine its modulation in macrophage inflammatory response in vitro. 
      Primary bone marrow-derived macrophages (BMDMs) from WT and Lif(-/-) mice were 
      isolated and stimulated with LPS to confirm the effect of Lif deletion on 
      macrophage inflammatory response. Supernatants from LIF and LPS-treated human 
      dental pulp cells (hDPCs) were collected and added to macrophages. Macrophage 
      chemotaxis was assessed using transwell assays. The results showed an increased 
      expression of LIF and LIFR with the progression of pulpitis, and LIFR was highly 
      expressed in macrophages. Lif deficiency alleviated experimental pulpitis with 
      the reduction of pro-inflammatory cytokines and macrophage infiltration. 
      Exogenous LIF promoted inflammatory response of LPS-induced macrophages through a 
      STAT3/p65-dependent pathway. Consistently, Lif deletion inhibited macrophage 
      inflammatory response in vitro. Supernatants of LIF-treated hDPCs enhanced 
      macrophage migration in LPS-induced inflammatory environment. Our findings 
      demonstrated that LIF aggravates pulpitis by promoting macrophage inflammatory 
      response through a STAT3/p65-dependent pathway. Furthermore, LIF plays a crucial 
      role in driving the recruitment of macrophages to inflamed pulp tissue by 
      promoting chemokine secretion in DPCs.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Guo, Donghua
AU  - Guo D
AD  - State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key 
      Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of 
      Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, 
      China.
FAU - Dong, Wei
AU  - Dong W
AD  - State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key 
      Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of 
      Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, 
      China.
FAU - Cong, Yaqi
AU  - Cong Y
AD  - State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key 
      Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of 
      Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, 
      China.
FAU - Liu, Yi
AU  - Liu Y
AD  - Department of Stomatology, Huangshi Central Hospital, Affiliated Hospital of 
      Hubei Polytechnic University, Edong Healthcare Group, Huangshi, China.
FAU - Liang, Youde
AU  - Liang Y
AD  - Yantian Hospital, Southern University of Science and Technology, Shenzhen, China.
FAU - Ye, Zhou
AU  - Ye Z
AD  - Applied Oral Sciences and Community Dental Care, Faculty of Dentistry, The 
      University of Hong Kong, Hong Kong, S.A.R, China.
FAU - Zhang, Jiali
AU  - Zhang J
AD  - State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key 
      Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of 
      Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, 
      China.
FAU - Zhou, Yi
AU  - Zhou Y
AD  - State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key 
      Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of 
      Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, 
      China. dryizhou@whu.edu.cn.
AD  - Center for Prosthodontics and Implant Dentistry, Optics Valley Branch, School and 
      Hospital of Stomatology, Wuhan University, Wuhan, China. dryizhou@whu.edu.cn.
LA  - eng
GR  - 82071090/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20231002
PL  - United States
TA  - Inflammation
JT  - Inflammation
JID - 7600105
RN  - 0 (Leukemia Inhibitory Factor)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (LIF protein, human)
RN  - 0 (Lif protein, mouse)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - Dental Pulp/metabolism
MH  - Inflammation/chemically induced/metabolism
MH  - Leukemia Inhibitory Factor/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/metabolism
MH  - *Pulpitis/metabolism
OTO - NOTNLM
OT  - Inflammation
OT  - Leukemia inhibitory factor
OT  - Macrophage
OT  - Pulpitis
EDAT- 2023/10/02 12:42
MHDA- 2024/01/22 06:42
CRDT- 2023/10/02 11:11
PHST- 2023/07/06 00:00 [received]
PHST- 2023/09/19 00:00 [accepted]
PHST- 2023/09/11 00:00 [revised]
PHST- 2024/01/22 06:42 [medline]
PHST- 2023/10/02 12:42 [pubmed]
PHST- 2023/10/02 11:11 [entrez]
AID - 10.1007/s10753-023-01910-6 [pii]
AID - 10.1007/s10753-023-01910-6 [doi]
PST - ppublish
SO  - Inflammation. 2024 Feb;47(1):307-322. doi: 10.1007/s10753-023-01910-6. Epub 2023 
      Oct 2.