PMID- 20386470
OWN - NLM
STAT- MEDLINE
DCOM- 20100916
LR  - 20181201
IS  - 1537-4513 (Electronic)
IS  - 1524-9557 (Linking)
VI  - 33
IP  - 4
DP  - 2010 May
TI  - Chemotherapeutic agents targeting the tubulin cytoskeleton modify LPS-induced 
      cytokine secretion by dendritic cells and increase antigen presentation.
PG  - 364-70
LID - 10.1097/CJI.0b013e3181cd1094 [doi]
AB  - Recent studies support the idea that certain chemotherapeutic agents do not act 
      only by cytotoxicity, but also have immunomodulatory activity. Because of their 
      role in mitosis chemotherapeutic agents targeting microtubules are widely used, 
      and this study determined the outcome of disturbing tubulin cytoskeleton dynamics 
      on human dendritic cell function. Dendritic cells (DCs) play a major role in the 
      generation of the adaptive immune response owing to their capacity for antigen 
      presentation leading to T lymphocyte activation and differentiation and there is 
      compelling evidence for their contribution to the antitumoral immune response. 
      Two agents that target the tubulin cytoskeleton were used, taxol and colchicine, 
      and a brief pretreatment with either increased antigen presentation by DCs 
      independently of significant phenotypic change, cell death, or cytokine 
      production. Although taxol and colchicine use different mechanisms to disrupt 
      microtubules, NF-kappabeta was activated by either. We therefore determined 
      whether the cytokine secretion profile in response to lipopolysaccharide (LPS) 
      was modified. LPS stimulation of DCs induced IL-10, IL-12p70, TNFalpha and 
      IL-1beta secretion, and taxol pretreatment modified this response by 
      down-regulating IL-1beta secretion whereas colchicine induced a proinflammatory 
      cytokine profile with reduced IL-10 and increased IL-12p70 and TNFalpha 
      secretion. Taken together, these data reveal new immunomodulatory strategies of 
      microtubule disrupting agents in dendritic cells, that of modifying the cytokine 
      response to LPS and that of increasing T lymphocyte activation without induction 
      of inflammatory cytokine secretion by dendritic cells.
FAU - Marin-Esteban, Viviana
AU  - Marin-Esteban V
AD  - Institut Universitaire d'Hematologie, Universite Paris-Diderot-Paris 7, INSERM 
      Unite 940, Hematologie, Immunologie, Cibles therapeutiques, Paris, France.
FAU - Charron, Dominique
AU  - Charron D
FAU - Gelin, Catherine
AU  - Gelin C
FAU - Mooney, Nuala
AU  - Mooney N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Tubulin)
RN  - P88XT4IS4D (Paclitaxel)
RN  - SML2Y3J35T (Colchicine)
SB  - IM
MH  - Antigen Presentation/drug effects
MH  - Antineoplastic Agents/*pharmacology
MH  - Cells, Cultured
MH  - Colchicine/*pharmacology
MH  - Cytokines/metabolism
MH  - Cytoskeleton/*drug effects
MH  - Dendritic Cells/*drug effects/*immunology/metabolism/pathology
MH  - Drug Interactions
MH  - Humans
MH  - Lipopolysaccharides/metabolism/pharmacology
MH  - Lymphocyte Activation/drug effects
MH  - NF-kappa B/metabolism
MH  - Neoplasms/*drug therapy/immunology
MH  - Paclitaxel/*pharmacology
MH  - T-Lymphocytes/immunology
MH  - Tubulin/metabolism
EDAT- 2010/04/14 06:00
MHDA- 2010/09/18 06:00
CRDT- 2010/04/14 06:00
PHST- 2010/04/14 06:00 [entrez]
PHST- 2010/04/14 06:00 [pubmed]
PHST- 2010/09/18 06:00 [medline]
AID - 10.1097/CJI.0b013e3181cd1094 [doi]
PST - ppublish
SO  - J Immunother. 2010 May;33(4):364-70. doi: 10.1097/CJI.0b013e3181cd1094.