PMID- 26266054
OWN - NLM
STAT- MEDLINE
DCOM- 20160419
LR  - 20181113
IS  - 1687-5443 (Electronic)
IS  - 2090-5904 (Print)
IS  - 1687-5443 (Linking)
VI  - 2015
DP  - 2015
TI  - Withaferin A Inhibits Nuclear Factor-kappaB-Dependent Pro-Inflammatory and Stress 
      Response Pathways in the Astrocytes.
PG  - 381964
LID - 10.1155/2015/381964 [doi]
LID - 381964
AB  - Several lines of evidence suggest that astrocytes play a key role in modulating 
      the immune responses of the central nervous system (CNS) to infections, injuries, 
      or pathologies. Yet, their contribution to these processes remains mostly 
      elusive. Astroglia are endowed with a wide range of toll-like receptors (TLR) by 
      which they can sense infectious agents as well as endogenous danger signals 
      released by damaged cells. Here we demonstrate that the activation of astrocytic 
      TLR4 by bacterial lipopolysaccharide (LPS) challenge can promote nuclear factor 
      kappaB (NF-kappaB)-dependent induction of pro-inflammatory and stress response mediators, 
      particularly Tumor Necrosis Factor alpha (TNFalpha), cyclooxygenase 2 (COX-2), and 
      inducible nitric oxide synthase (iNOS). Since the steroid lactone Withaferin A 
      was described to inhibit NF-kappaB activity in different cell types, we next 
      determined the impact of this natural compound towards the identified astrocytic 
      signalling pathway. Innate immune activation was induced by stimulation of the 
      LPS/TLR4 axis in spinal cord astrocytes. We provide evidence that both 
      pre-treating and post-treating the cells with Withaferin A attenuate astrocytic 
      NF-kappaB activity as well as the consequent production of TNFalpha, COX-2, and iNOS 
      induced by stimulation of the LPS/TLR4 pathway. This study suggests that 
      Withaferin A may be an eligible candidate for the treatment of neuroinflammatory 
      and stress conditions characterized by an important astrocytic input.
FAU - Martorana, Francesca
AU  - Martorana F
AD  - Laboratory for Research on Neurodegenerative Disorders, IRCCS Fondazione 
      Salvatore Maugeri, 27100 Pavia, Italy.
FAU - Guidotti, Giulia
AU  - Guidotti G
AD  - Laboratory for Research on Neurodegenerative Disorders, IRCCS Fondazione 
      Salvatore Maugeri, 27100 Pavia, Italy.
FAU - Brambilla, Liliana
AU  - Brambilla L
AD  - Laboratory for Research on Neurodegenerative Disorders, IRCCS Fondazione 
      Salvatore Maugeri, 27100 Pavia, Italy.
FAU - Rossi, Daniela
AU  - Rossi D
AD  - Laboratory for Research on Neurodegenerative Disorders, IRCCS Fondazione 
      Salvatore Maugeri, 27100 Pavia, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150721
PL  - United States
TA  - Neural Plast
JT  - Neural plasticity
JID - 100883417
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B p50 Subunit)
RN  - 0 (NFKB1 protein, human)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Withanolides)
RN  - EC 1.14.13.39 (NOS2 protein, human)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
RN  - L6DO3QW4K5 (withaferin A)
SB  - IM
MH  - Antineoplastic Agents, Phytogenic/*pharmacology
MH  - Astrocytes/*drug effects
MH  - Cell Line, Tumor
MH  - Cyclooxygenase 2/genetics
MH  - Encephalitis/*physiopathology
MH  - Humans
MH  - Lipopolysaccharides/pharmacology
MH  - NF-kappa B p50 Subunit/*antagonists & inhibitors
MH  - Nitric Oxide Synthase Type II/genetics
MH  - Signal Transduction/drug effects
MH  - Spinal Cord/cytology/drug effects
MH  - Stress, Psychological/*physiopathology
MH  - Toll-Like Receptor 4/drug effects/metabolism
MH  - Tumor Necrosis Factor-alpha/genetics
MH  - Withanolides/*pharmacology
PMC - PMC4523683
EDAT- 2015/08/13 06:00
MHDA- 2016/04/20 06:00
PMCR- 2015/07/21
CRDT- 2015/08/13 06:00
PHST- 2015/02/27 00:00 [received]
PHST- 2015/07/01 00:00 [revised]
PHST- 2015/07/02 00:00 [accepted]
PHST- 2015/08/13 06:00 [entrez]
PHST- 2015/08/13 06:00 [pubmed]
PHST- 2016/04/20 06:00 [medline]
PHST- 2015/07/21 00:00 [pmc-release]
AID - 10.1155/2015/381964 [doi]
PST - ppublish
SO  - Neural Plast. 2015;2015:381964. doi: 10.1155/2015/381964. Epub 2015 Jul 21.