PMID- 31535738
OWN - NLM
STAT- MEDLINE
DCOM- 20201027
LR  - 20201027
IS  - 1600-0625 (Electronic)
IS  - 0906-6705 (Linking)
VI  - 28
IP  - 11
DP  - 2019 Nov
TI  - S-allyl cysteine inhibits TNF-alpha-induced inflammation in HaCaT keratinocytes by 
      inhibition of NF- kappaB-dependent gene expression via sustained ERK activation.
PG  - 1328-1335
LID - 10.1111/exd.14041 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha)-induced keratinocyte inflammation plays a key 
      role in the pathogenesis of multiple inflammatory skin diseases. Here we 
      investigated the anti-inflammatory effect of S-allyl cysteine (SAC) on 
      TNF-alpha-induced HaCaT keratinocyte cells and the mechanism behind its 
      anti-inflammatory potential. SAC was found to inhibit TNF-alpha-stimulated cytokine 
      expression. Further, SAC was found to inhibit TNF-alpha-induced activation of p38, 
      JNK and NF-kappaB pathways. Interestingly, SAC was found to differentially regulate 
      ERK MAP kinase in cells. TNF-alpha-induced transient ERK activation and SAC treatment 
      resulted in sustained ERK activation both in the presence and absence of TNF-alpha. 
      Additionally, SAC failed to inhibit the TNF-alpha-induced expression of the 
      pro-inflammatory cytokines TNF-alpha and IL-1beta when cells were treated with the MEK 
      inhibitor PD98059, suggesting that the anti-inflammatory effect of SAC is via 
      sustained activation of the ERK pathway. Since ERK activation has been reported 
      to negatively regulate NF-kappaB-driven gene expression and we find that SAC 
      activates ERK and negatively regulates NF-kappaB, we investigated whether there 
      existed any crosstalk between the ERK and the NF-kappaB pathways. NF-kappaB-dependent 
      reporter assay, visualization of the nuclear translocation of NF-kappaB-p65 subunit 
      and determination of the cellular levels of I-kappaB, the inhibitor of NF-kappaB, 
      revealed that SAC inhibited TNF-alpha-induced NF-kappaB activation, and PD98059 treatment 
      reversed this effect. These results collectively suggest that SAC inhibits 
      TNF-alpha-induced inflammation in HaCaT cells via a combined effect entailing the 
      inhibition of the p38 and the JNK pathways and NF-kappaB pathway via the sustained 
      activation of ERK.
CI  - (c) 2019 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.
FAU - Basu, Chitra
AU  - Basu C
AD  - Department of Biophysics, Molecular Biology and Bioinformatics, University of 
      Calcutta, Kolkata, India.
FAU - Chatterjee, Abhipriya
AU  - Chatterjee A
AD  - Department of Biophysics, Molecular Biology and Bioinformatics, University of 
      Calcutta, Kolkata, India.
FAU - Bhattacharya, Sampurna
AU  - Bhattacharya S
AD  - Department of Biophysics, Molecular Biology and Bioinformatics, University of 
      Calcutta, Kolkata, India.
FAU - Dutta, Naibedya
AU  - Dutta N
AD  - Division of Molecular Medicine, Bose Institute, Kolkata, India.
FAU - Sur, Runa
AU  - Sur R
AUID- ORCID: 0000-0001-8399-2508
AD  - Department of Biophysics, Molecular Biology and Bioinformatics, University of 
      Calcutta, Kolkata, India.
LA  - eng
GR  - University of Calcutta/International
GR  - DST-FIST facility/International
GR  - University Grant Commission/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190929
PL  - Denmark
TA  - Exp Dermatol
JT  - Experimental dermatology
JID - 9301549
RN  - 0 (Interleukin-1beta)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 81R3X99M15 (S-allylcysteine)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Cell Line, Transformed
MH  - Cysteine/*analogs & derivatives/metabolism
MH  - Humans
MH  - Interleukin-1beta/metabolism
MH  - Keratinocytes/*metabolism
MH  - MAP Kinase Signaling System
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - NF-kappa B/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - ERK
OT  - NF-kappaB
OT  - TNF-alpha
OT  - inflammation
OT  - keratinocytes
EDAT- 2019/09/20 06:00
MHDA- 2020/10/28 06:00
CRDT- 2019/09/20 06:00
PHST- 2019/03/25 00:00 [received]
PHST- 2019/08/27 00:00 [revised]
PHST- 2019/09/15 00:00 [accepted]
PHST- 2019/09/20 06:00 [pubmed]
PHST- 2020/10/28 06:00 [medline]
PHST- 2019/09/20 06:00 [entrez]
AID - 10.1111/exd.14041 [doi]
PST - ppublish
SO  - Exp Dermatol. 2019 Nov;28(11):1328-1335. doi: 10.1111/exd.14041. Epub 2019 Sep 
      29.