PMID- 23360889
OWN - NLM
STAT- MEDLINE
DCOM- 20130705
LR  - 20220316
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 268
IP  - 1
DP  - 2013 Apr 1
TI  - Involvement of PKA and HO-1 signaling in anti-inflammatory effects of surfactin 
      in BV-2 microglial cells.
PG  - 68-78
LID - S0041-008X(13)00038-0 [pii]
LID - 10.1016/j.taap.2013.01.017 [doi]
AB  - Surfactin, one of the most powerful biosurfactants, is a bacterial cyclic 
      lipopeptide. Here, we investigated the anti-neuroinflammatory properties of 
      surfactin in lipoteichoic acid (LTA)-stimulated BV-2 microglial cells. Surfactin 
      significantly inhibited excessive production of the pro-inflammatory mediators 
      TNF-alpha, IL-1beta, IL-6, monocyte chemoattractant protein-1 (MCP-1), prostaglandin E2 
      (PGE2), nitric oxide (NO) and reactive oxygen species (ROS), and suppressed the 
      expression of matrix metalloproteinase-9 (MMP-9), inducible NO synthase (iNOS) 
      and cyclooxygenase-2 (COX-2). Subsequent mechanistic studies revealed that 
      surfactin inhibited LTA-induced nuclear factor-kappaB (NF-kappaB) and signal 
      transducer and activator of transcription-1 (STAT-1) activation. However, 
      surfactin increases the phosphorylation of the STAT-3, a component of the 
      homeostatic mechanism causing anti-inflammatory events. We also demonstrated that 
      surfactin induces heme oxygenase-1 (HO-1) expression and nuclear factor-regulated 
      factor-2 (Nrf-2) activation, and that the anti-inflammatory effects of surfactin 
      are abrogated by small interfering RNA-mediated knock-down of HO-1 or Nrf-2. 
      Interestingly, we found that surfactin increased the level of cAMP and induced 
      phosphorylation of cAMP responsive element binding protein (CREB) in microglial 
      cells. Furthermore, treatment with the protein kinase A (PKA) inhibitor, H-89, 
      blocked HO-1 induction by surfactin and abolished surfactin's suppressive effects 
      on ROS and NO production. These results indicate that HO-1 and its upstream 
      effector, PKA, play a pivotal role in the anti-neuroinflammatory response of 
      surfactin in LTA-stimulated microglia. Therefore, surfactin might have 
      therapeutic potential for neuroprotective agents to treat inflammatory and 
      neurodegenerative diseases.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Park, Sun Young
AU  - Park SY
AD  - Department of Molecular Biology, Pusan National University, Jangjeon-dong, 
      Keumjeong-gu, Busan, Republic of Korea.
FAU - Kim, Ji-Hee
AU  - Kim JH
FAU - Lee, Sang Joon
AU  - Lee SJ
FAU - Kim, YoungHee
AU  - Kim Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130127
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (Lipopeptides)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NF-kappa B)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (Peptides, Cyclic)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT3 Transcription Factor)
RN  - 24730-31-2 (surfactin peptide)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Blotting, Western
MH  - Brain/cytology/drug effects/metabolism
MH  - Cell Survival/drug effects
MH  - Cyclic AMP-Dependent Protein Kinases/*metabolism
MH  - Cytokines/metabolism
MH  - Heme Oxygenase-1/*metabolism
MH  - Lipopeptides/*pharmacology
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Microglia/*drug effects/*metabolism
MH  - Microscopy, Confocal
MH  - NF-E2-Related Factor 2/immunology
MH  - NF-kappa B/metabolism
MH  - Peptides, Cyclic/*pharmacology
MH  - STAT1 Transcription Factor/metabolism
MH  - STAT3 Transcription Factor/metabolism
MH  - Signal Transduction/drug effects
EDAT- 2013/01/31 06:00
MHDA- 2013/07/06 06:00
CRDT- 2013/01/31 06:00
PHST- 2012/09/24 00:00 [received]
PHST- 2013/01/08 00:00 [revised]
PHST- 2013/01/12 00:00 [accepted]
PHST- 2013/01/31 06:00 [entrez]
PHST- 2013/01/31 06:00 [pubmed]
PHST- 2013/07/06 06:00 [medline]
AID - S0041-008X(13)00038-0 [pii]
AID - 10.1016/j.taap.2013.01.017 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2013 Apr 1;268(1):68-78. doi: 10.1016/j.taap.2013.01.017. 
      Epub 2013 Jan 27.