PMID- 36191359
OWN - NLM
STAT- MEDLINE
DCOM- 20221013
LR  - 20221116
IS  - 1096-0023 (Electronic)
IS  - 1043-4666 (Linking)
VI  - 160
DP  - 2022 Dec
TI  - Nicotine ameliorates inflammatory mediators in RU486 induced preterm labor model 
      through activating cholinergic anti-inflammatory pathway.
PG  - 156054
LID - S1043-4666(22)00263-0 [pii]
LID - 10.1016/j.cyto.2022.156054 [doi]
AB  - BACKGROUND: Preterm birth is a global public health threat. Inflammatory reaction 
      is thought to mediate preterm birth. The role of nicotine, an anti-inflammatory 
      agent that is mediated by cholinergic anti-inflammatory pathways (CAP), remains 
      unclear in the pathogenesis. METHODS: Pregnant rats were randomly divided into 
      four groups (20 rats each): pregnant control group (P), RU486-treated group 
      (PTL), RU486 and nicotine-treated group (PTL + N), RU486, nicotine and alpha-BGT 
      treated group (PTL + N + A). Rats were administered RU486 (1.0 mg/kg) by 
      subcutaneous injection on gestational day (GD) 18 to establish PTL model. 
      Subcutaneous injection of nicotine (1 mg/kg) was administered daily from GD 16 to 
      18. alpha-BGT (1 microg/kg) was administrated subcutaneously in two sessions and each 
      session was 30 min prior to nicotine. TNF-alpha, IL-1beta, IL-4, IL-6, IL-10 in 
      myometrium and serum were detected by Luminex. Macrophage infiltration and 
      alpha7nAChR were detected by IHC. RESULTS: We established a RU486-induced preterm 
      labor rat model. Preterm labor was associated with a striking upregulation 
      inflammatory mediators and increased macrophage infiltration. Nicotine 
      significantly prolonged gestation (P < 0.05) and alpha-BGT treatment reversed the 
      prolonged interval (P < 0.05). The cytokines all markedly elevated at 12 h, 
      but deceased after delivery (P < 0.05). The IL-1beta and TNF-alpha in serum were 
      significantly increased in PTL group vs P group (P < 0.05), and decreased 
      after nicotine treatment (P < 0.05). The cytokines IL-1beta, IL-4, IL-6, IL-10 
      and TNF-alpha in myometrium increased as the same trend as in serum. Nicotine 
      treatment also downregulated the expression of alpha7nAChR in pregnant tissue. 
      CONCLUSION: We confirmed the increased inflammation in preterm birth. Nicotine 
      was able to down-regulate the inflammatory mediates and prolong the pregnant 
      duration in PTL model, which might be induced by activating alpha7nAChR through CAP. 
      This study provides a novel evidence supporting the future development of 
      therapeutic target for preterm birth.
CI  - Copyright (c) 2022. Published by Elsevier Ltd.
FAU - Huang, Qian
AU  - Huang Q
AD  - Department of Obstetrics, Guangzhou Women and Children's Medical Center, 
      Guangzhou Medical University, Guangzhou, China.
FAU - Ye, Aihua
AU  - Ye A
AD  - Department of Obstetrics and Gynecology, The Maternal and Child Health Hospital 
      of Longhua District, Shenzhen, China.
FAU - Li, Pin
AU  - Li P
AD  - Department of Obstetrics, Guangzhou Women and Children's Medical Center, 
      Guangzhou Medical University, Guangzhou, China.
FAU - Bao, Junjie
AU  - Bao J
AD  - Department of Obstetrics, Guangzhou Women and Children's Medical Center, 
      Guangzhou Medical University, Guangzhou, China.
FAU - Garfield, Robert E
AU  - Garfield RE
AD  - University of Arizona College of Medicine, Phoenix, AZ, USA.
FAU - Liu, Huishu
AU  - Liu H
AD  - Department of Obstetrics, Guangzhou Women and Children's Medical Center, 
      Guangzhou Medical University, Guangzhou, China. Electronic address: 
      huishuliu@hotmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221001
PL  - England
TA  - Cytokine
JT  - Cytokine
JID - 9005353
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (alpha7 Nicotinic Acetylcholine Receptor)
RN  - 130068-27-8 (Interleukin-10)
RN  - 207137-56-2 (Interleukin-4)
RN  - 320T6RNW1F (Mifepristone)
RN  - 6M3C89ZY6R (Nicotine)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents
MH  - Cytokines/metabolism
MH  - Female
MH  - Inflammation/metabolism
MH  - Inflammation Mediators
MH  - Interleukin-10/metabolism
MH  - Interleukin-4/metabolism
MH  - Interleukin-6/metabolism
MH  - Mifepristone
MH  - Neuroimmunomodulation
MH  - Nicotine
MH  - *Obstetric Labor, Premature/chemically induced/drug therapy
MH  - Pregnancy
MH  - Premature Birth
MH  - Rats
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - alpha7 Nicotinic Acetylcholine Receptor
OTO - NOTNLM
OT  - Cholinergic anti-inflammatory pathway
OT  - Inflammtion
OT  - Macrophage
OT  - Nicotine
OT  - Preterm labor
OT  - alpha7nAChR
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/10/04 06:00
MHDA- 2022/10/14 06:00
CRDT- 2022/10/03 18:13
PHST- 2022/06/12 00:00 [received]
PHST- 2022/09/02 00:00 [revised]
PHST- 2022/09/13 00:00 [accepted]
PHST- 2022/10/04 06:00 [pubmed]
PHST- 2022/10/14 06:00 [medline]
PHST- 2022/10/03 18:13 [entrez]
AID - S1043-4666(22)00263-0 [pii]
AID - 10.1016/j.cyto.2022.156054 [doi]
PST - ppublish
SO  - Cytokine. 2022 Dec;160:156054. doi: 10.1016/j.cyto.2022.156054. Epub 2022 Oct 1.