PMID- 36917739
OWN - NLM
STAT- MEDLINE
DCOM- 20230414
LR  - 20230423
IS  - 2162-3279 (Electronic)
VI  - 13
IP  - 4
DP  - 2023 Apr
TI  - Fingolimod ameliorates chronic experimental autoimmune neuritis by modulating 
      inflammatory cytokines and Akt/mTOR/NF-kappaB signaling.
PG  - e2965
LID - 10.1002/brb3.2965 [doi]
LID - e2965
AB  - OBJECTIVE: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an 
      immune-mediated disease that targets the myelin sheaths of the peripheral nerves. 
      Fingolimod is a sphingosine 1 phosphate (S1P) receptor antagonist with a high 
      affinity for S1P receptors through the Akt-mTOR pathway, and prior research has 
      suggested that it might be helpful in autoimmune illnesses. METHODS: Chronic 
      experimental autoimmune neuritis (c-EAN) was induced by immunizing Lewis rats 
      with the S-palm P0(180-199) peptide, and then the treatment group was 
      intraperitoneally injected with fingolimod (1 mg/kg) daily. Hematoxylin and eosin 
      staining was used to assess the severity of nerve injury. Immunohistochemistry 
      staining showed that fingolimod's anti-inflammatory effects on c-EAN rats might 
      be realized through the NF-kappaB signaling pathway. Tumor necrosis factor-alpha (TNF-alpha), 
      interferon-gamma (INF-gamma), interleukin-1beta (IL-1beta), interleukin 6 (IL-6), inducible 
      nitric oxide synthase (iNOS), and intercellular adhesion molecule-1 (ICAM-1) were 
      measured to evaluate the inflammation levels, and pAkt, p-S6, and p-p65 were used 
      to measure the abundance of downstream activation markers to determine whether 
      the Akt/mTOR/NF-kappaB signaling pathway was activated in the c-EAN model. RESULTS: 
      Fingolimod treatment reduced the inflammatory reaction and the expression of 
      NF-kappaB in sciatic nerves. It also decreased the mRNA levels of the proinflammatory 
      cytokines TNF-alpha, IFN-gamma, IL-1beta, IL-6, iNOS, and ICAM-1 and pAkt, p-S6, and p-p65, 
      representing the Akt/mTOR/NF-kappaB signaling pathway. CONCLUSION: Our data showed 
      that fingolimod could improve the disease course, alleviate the decrease in 
      inflammation, and reduce proinflammatory cytokines through the Akt/mTOR/NF-kappaB 
      axis in c-EAN rats, which could be beneficial for the development of CIDP-related 
      research.
CI  - (c) 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.
FAU - Feng, Yuan
AU  - Feng Y
AD  - Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China.
AD  - Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China.
FAU - Feng, Fang
AU  - Feng F
AD  - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Pan, Shuyi
AU  - Pan S
AD  - Department of Hyperbaric Medicine, 6th Medical Center of PLA General Hospital, 
      Beijing, China.
FAU - Zhang, Jiewen
AU  - Zhang J
AD  - Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China.
FAU - Li, Wei
AU  - Li W
AD  - Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230314
PL  - United States
TA  - Brain Behav
JT  - Brain and behavior
JID - 101570837
RN  - 0 (Cytokines)
RN  - 0 (NF-kappa B)
RN  - G926EC510T (Fingolimod Hydrochloride)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Interleukin-6)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.1.1 (mTOR protein, rat)
SB  - IM
MH  - Rats
MH  - Animals
MH  - Cytokines/metabolism
MH  - NF-kappa B/metabolism
MH  - Fingolimod Hydrochloride/adverse effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Intercellular Adhesion Molecule-1/adverse effects/genetics
MH  - Tumor Necrosis Factor-alpha
MH  - Interleukin-6
MH  - *Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
MH  - *Neuritis, Autoimmune, Experimental/drug therapy
MH  - Rats, Inbred Lew
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/adverse effects/metabolism
MH  - Inflammation/drug therapy
PMC - PMC10097075
OTO - NOTNLM
OT  - NF-kappaB
OT  - chronic experimental autoimmune neuritis
OT  - chronic inflammatory demyelinating polyradiculoneuropathy
OT  - fingolimod
OT  - peripheral neuropathy
COIS- The authors declare no conflicts of interest.
EDAT- 2023/03/15 06:00
MHDA- 2023/04/14 06:42
PMCR- 2023/03/14
CRDT- 2023/03/14 15:42
PHST- 2023/02/14 00:00 [revised]
PHST- 2022/12/27 00:00 [received]
PHST- 2023/02/17 00:00 [accepted]
PHST- 2023/04/14 06:42 [medline]
PHST- 2023/03/15 06:00 [pubmed]
PHST- 2023/03/14 15:42 [entrez]
PHST- 2023/03/14 00:00 [pmc-release]
AID - BRB32965 [pii]
AID - 10.1002/brb3.2965 [doi]
PST - ppublish
SO  - Brain Behav. 2023 Apr;13(4):e2965. doi: 10.1002/brb3.2965. Epub 2023 Mar 14.