PMID- 26914888
OWN - NLM
STAT- MEDLINE
DCOM- 20170105
LR  - 20220321
IS  - 1600-079X (Electronic)
IS  - 0742-3098 (Linking)
VI  - 60
IP  - 4
DP  - 2016 May
TI  - JNK-TLR9 signal pathway mediates allergic airway inflammation through suppressing 
      melatonin biosynthesis.
PG  - 415-23
LID - 10.1111/jpi.12323 [doi]
AB  - Toll-like receptors (TLRs) play pivotal role in the pathogenesis of allergic 
      airway diseases such as asthma. TLR9 is one of the most extensively studied TLRs 
      as an approach to treat asthma. In this study, we investigated the role of TLR9 
      in the allergic airway inflammation and the underlying mechanism. Wild-type (WT) 
      mice and TLR9(-/-) mice were sensitized and challenged with OVA to establish 
      allergic airway disease model. We found that the expression of TLR9 was elevated 
      concomitantly with airway inflammation post-OVA challenge, and TLR9 deficiency 
      effectively inhibited airway inflammation, including serum OVA-specific 
      immunoglobulin E (IgE), pulmonary inflammatory cell recruitment, mucus secretion, 
      and bronchoalveolar lavage fluid (BALF) inflammatory cytokine production. 
      Meanwhile, the protein expression of hydroxyindole-o-methyltransferase (HIOMT) in 
      lung tissues, the level of melatonin in serum, and BALF were reduced in 
      OVA-challenged WT mice, while these reductions were significantly restored by 
      TLR9 deficiency. Additionally, we showed that although TLR9 deficiency had no 
      effect on OVA-induced phosphorylation of JNK, inhibition of JNK by specific 
      inhibitor SP600125 significantly decreased OVA-induced expression of TLR9, 
      suggesting that JNK is the upstream signal molecular of TLR9. Furthermore, 
      SP600125 treatment promoted resolution of allergic airway inflammation in 
      OVA-challenged WT mice, but not further ameliorated allergic airway inflammation 
      in OVA-challenged TLR9(-/-) mice. Similarly, SP600125 significantly restored the 
      protein expression of HIOMT and the level of melatonin in OVA-challenged WT mice, 
      while such effect was not further enhanced by TLR9 deficiency. Collectively, our 
      results indicated that JNK-TLR9 signal pathway mediates allergic airway 
      inflammation through suppressing melatonin biosynthesis.
CI  - (c) 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Wu, Hui-Mei
AU  - Wu HM
AD  - Anhui Geriatric Institute, Department of Pulmonary, The First Affiliated Hospital 
      of Anhui Medical University, Hefei, Anhui, China.
FAU - Shen, Qi-Ying
AU  - Shen QY
AD  - Anhui Geriatric Institute, Department of Pulmonary, The First Affiliated Hospital 
      of Anhui Medical University, Hefei, Anhui, China.
FAU - Fang, Lei
AU  - Fang L
AD  - Anhui Geriatric Institute, Department of Pulmonary, The First Affiliated Hospital 
      of Anhui Medical University, Hefei, Anhui, China.
FAU - Zhang, Shi-Hai
AU  - Zhang SH
AD  - Anhui Geriatric Institute, Department of Pulmonary, The First Affiliated Hospital 
      of Anhui Medical University, Hefei, Anhui, China.
FAU - Shen, Pei-Ting
AU  - Shen PT
AD  - Anhui Geriatric Institute, Department of Pulmonary, The First Affiliated Hospital 
      of Anhui Medical University, Hefei, Anhui, China.
FAU - Liu, Ya-Jing
AU  - Liu YJ
AD  - Center for Reproductive Medicine, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, Anhui, China.
FAU - Liu, Rong-Yu
AU  - Liu RY
AD  - Anhui Geriatric Institute, Department of Pulmonary, The First Affiliated Hospital 
      of Anhui Medical University, Hefei, Anhui, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160309
PL  - England
TA  - J Pineal Res
JT  - Journal of pineal research
JID - 8504412
RN  - 0 (Tlr9 protein, mouse)
RN  - 0 (Toll-Like Receptor 9)
RN  - JL5DK93RCL (Melatonin)
SB  - IM
MH  - Animals
MH  - Asthma/*metabolism
MH  - Blotting, Western
MH  - Disease Models, Animal
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Hypersensitivity/metabolism
MH  - MAP Kinase Signaling System/*physiology
MH  - Melatonin/*biosynthesis
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Pneumonia/*metabolism
MH  - Toll-Like Receptor 9/*metabolism
OTO - NOTNLM
OT  - TLR9
OT  - allergic airway inflammation
OT  - c-Jun NH2 terminal kinase
OT  - melatonin synthesis
OT  - signal pathway
EDAT- 2016/02/26 06:00
MHDA- 2017/01/06 06:00
CRDT- 2016/02/26 06:00
PHST- 2015/12/31 00:00 [received]
PHST- 2016/02/18 00:00 [accepted]
PHST- 2016/02/26 06:00 [entrez]
PHST- 2016/02/26 06:00 [pubmed]
PHST- 2017/01/06 06:00 [medline]
AID - 10.1111/jpi.12323 [doi]
PST - ppublish
SO  - J Pineal Res. 2016 May;60(4):415-23. doi: 10.1111/jpi.12323. Epub 2016 Mar 9.