PMID- 34872043
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240220
IS  - 2213-2317 (Electronic)
IS  - 2213-2317 (Linking)
VI  - 48
DP  - 2021 Dec 1
TI  - 1,25-Dihydroxyvitamin D(3) attenuates IL-1beta secretion by suppressing NLRP1 
      inflammasome activation by upregulating the NRF2-HO-1 pathway in epidermal 
      keratinocytes.
PG  - 102203
LID - S2213-2317(21)00363-3 [pii]
LID - 10.1016/j.redox.2021.102203 [doi]
LID - 102203
AB  - The nucleotide-binding oligomerization domain-like receptor family pyrin 
      domain-containing protein (NLRP) inflammasome is a key inflammatory signaling 
      pathway activated via a two-step signaling process consisting of priming and 
      activation steps. Several studies have shown that 1,25-dihydroxyvitamin D3 
      (1,25(OH)(2)VD(3)) inhibits the priming step required for NLRP3 inflammasome 
      activation in immune cells. However, as activating the NLRP1 inflammasome in 
      keratinocytes does not necessarily require a priming step, whether 
      1,25(OH)(2)VD(3) inhibits NLRP1 activation in unprimed keratinocytes is currently 
      unknown. In this study, we showed that 1,25(OH)(2)VD(3) inhibits 
      nigericin-induced NLRP1 inflammasome activation in unprimed keratinocytes. 
      1,25(OH)(2)VD(3) suppressed nigericin-induced interleukin-1beta (IL-1beta) secretion 
      and caspase-1 activation in human primary keratinocytes. In addition, 
      1,25(OH)(2)VD(3) significantly inhibited the formation of apoptosis-associated 
      speck-like protein containing a caspase recruitment domain (ASC) oligomers and 
      specks, but not caspase-1 enzymatic activity, suggesting that 1,25(OH)(2)VD(3) 
      prevents NLRP1-ASC complex assembly in keratinocytes. Vitamin D receptor 
      (VDR)-knockdown abolished the inhibitory effects of 1,25(OH)(2)VD(3) on 
      nigericin-induced ASC oligomerization and IL-1beta secretion, suggesting that 
      1,25(OH)(2)VD(3) suppresses inflammasome activation via VDR signaling. 
      Furthermore, nigericin induced K(+) efflux and cellular reactive oxygen species 
      (ROS) production, and 1,25(OH)(2)VD(3) pretreatment suppressed nigericin-induced 
      ROS production. 1,25(OH)(2)VD(3) increased the expression of both nuclear factor 
      erythroid 2-related factor 2 (NRF2) and heme oxygenase-1 (HO-1), whereas HO-1 
      inhibition or NRF2 and HO-1 knockdown abrogated the inhibitory effects of 
      1,25(OH)(2)VD(3) on IL-1beta secretion. Our results indicate that 1,25(OH)(2)VD(3) 
      inhibits nigericin-induced activation step of NLRP1 inflammasome activation in 
      unprimed keratinocytes. Our findings reveal the mechanism underlying the 
      inhibitory effect of 1,25(OH)(2)VD(3), which involves NRF2-HO-1 pathway 
      activation through the VDR, providing further insight into the potential function 
      of 1,25(OH)(2)VD(3) as a therapeutic agent for inflammasome-related skin 
      diseases.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Nakajo, Takahisa
AU  - Nakajo T
AD  - DHC Corporation Laboratories, Division 2, 2-42 Hamada, Mihama-ku, Chiba, 
      261-0025, Japan. Electronic address: tnakajo@dhc.co.jp.
FAU - Katayoshi, Takeshi
AU  - Katayoshi T
AD  - DHC Corporation Laboratories, Division 2, 2-42 Hamada, Mihama-ku, Chiba, 
      261-0025, Japan. Electronic address: t-katayoshi@dhc.co.jp.
FAU - Kitajima, Natsuko
AU  - Kitajima N
AD  - DHC Corporation Laboratories, Division 2, 2-42 Hamada, Mihama-ku, Chiba, 
      261-0025, Japan. Electronic address: nkitajima@dhc.co.jp.
FAU - Tsuji-Naito, Kentaro
AU  - Tsuji-Naito K
AD  - DHC Corporation Laboratories, Division 2, 2-42 Hamada, Mihama-ku, Chiba, 
      261-0025, Japan. Electronic address: knaito@dhc.co.jp.
LA  - eng
PT  - Journal Article
DEP - 20211201
PL  - Netherlands
TA  - Redox Biol
JT  - Redox biology
JID - 101605639
SB  - IM
PMC - PMC8646996
OTO - NOTNLM
OT  - IL-1beta
OT  - Inflammasome
OT  - NRF2-HO-1 pathway
OT  - Normal human epidermal keratinocytes
OT  - Reactive oxygen species
OT  - Vitamin D
EDAT- 2021/12/07 06:00
MHDA- 2021/12/07 06:01
PMCR- 2021/12/01
CRDT- 2021/12/06 20:28
PHST- 2021/07/21 00:00 [received]
PHST- 2021/11/24 00:00 [revised]
PHST- 2021/11/29 00:00 [accepted]
PHST- 2021/12/07 06:01 [medline]
PHST- 2021/12/07 06:00 [pubmed]
PHST- 2021/12/06 20:28 [entrez]
PHST- 2021/12/01 00:00 [pmc-release]
AID - S2213-2317(21)00363-3 [pii]
AID - 102203 [pii]
AID - 10.1016/j.redox.2021.102203 [doi]
PST - aheadofprint
SO  - Redox Biol. 2021 Dec 1;48:102203. doi: 10.1016/j.redox.2021.102203.