PMID- 22972370
OWN - NLM
STAT- MEDLINE
DCOM- 20130317
LR  - 20161125
IS  - 1529-0131 (Electronic)
IS  - 0004-3591 (Linking)
VI  - 65
IP  - 1
DP  - 2013 Jan
TI  - Blocking of p38 and transforming growth factor beta receptor pathways impairs the 
      ability of tolerogenic dendritic cells to suppress murine arthritis.
PG  - 120-9
LID - 10.1002/art.37702 [doi]
AB  - OBJECTIVE: Dendritic cells (DCs) modulated with lipopolysaccharide (LPS) are able 
      to reduce inflammation when therapeutically administered into mice with 
      collagen-induced arthritis (CIA). The aim of this study was to uncover the 
      mechanisms that define the tolerogenic effect of short-term LPS-modulated DCs on 
      CIA. METHODS: Bone marrow-derived DCs were stimulated for 4 hours with LPS and 
      characterized for their expression of maturation markers and their cytokine 
      secretion profiles. Stimulated cells were treated with SB203580 or SB431542 to 
      inhibit the p38 or transforming growth factor beta (TGFbeta) receptor pathway, 
      respectively, or were left unmodified and, on day 35 after CIA induction, were 
      used to inoculate mice. Disease severity was evaluated clinically. CD4+ T cell 
      populations were counted in the spleen and lymph nodes from inoculated or 
      untreated mice with CIA. CD4+ splenic T cells were transferred from mice with CIA 
      treated with LPS-stimulated DCs or from untreated mice with CIA into other mice 
      with CIA on day 35 of arthritis. RESULTS: Treatment with LPS-stimulated DCs 
      increased the numbers of interleukin-10 (IL-10)-secreting and TGFbeta-secreting CD4+ 
      T cells, but decreased the numbers of Th17 cells. Adoptive transfer of CD4+ T 
      cells from treated mice with CIA reproduced the inhibition of active CIA 
      accomplished with LPS-stimulated DCs. The therapeutic effect of LPS-stimulated 
      DCs and their influence on T cell populations were abolished when the p38 and the 
      TGFbeta receptor pathways were inhibited. CONCLUSION: DCs modulated short-term (4 
      hours) with LPS are able to confer a sustained cure in mice with established 
      arthritis by re-educating the CD4+ T cell populations. This effect is dependent 
      on the p38 and the TGFbeta receptor signaling pathways, which suggests the 
      participation of IL-10 and TGFbeta in the recovery of tolerance.
CI  - Copyright (c) 2013 by the American College of Rheumatology.
FAU - Garate, David
AU  - Garate D
AD  - University of Chile and Millennium Institute on Immunology and Immunotherapy, 
      Santiago, Chile.
FAU - Rojas-Colonelli, Nicole
AU  - Rojas-Colonelli N
FAU - Pena, Corina
AU  - Pena C
FAU - Salazar, Lorena
AU  - Salazar L
FAU - Abello, Paula
AU  - Abello P
FAU - Pesce, Barbara
AU  - Pesce B
FAU - Aravena, Octavio
AU  - Aravena O
FAU - Garcia-Gonzalez, Paulina
AU  - Garcia-Gonzalez P
FAU - Ribeiro, Carolina H
AU  - Ribeiro CH
FAU - Molina, Maria C
AU  - Molina MC
FAU - Catalan, Diego
AU  - Catalan D
FAU - Aguillon, Juan C
AU  - Aguillon JC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide)
RN  - 0 (Benzamides)
RN  - 0 (Dioxoles)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Imidazoles)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, Transforming Growth Factor beta)
RN  - OU13V1EYWQ (SB 203580)
SB  - IM
MH  - Animals
MH  - Arthritis, Experimental/*immunology/metabolism/pathology
MH  - Benzamides/pharmacology
MH  - CD4-Positive T-Lymphocytes/*immunology/metabolism/pathology
MH  - Dendritic Cells/*immunology/metabolism/pathology
MH  - Dioxoles/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Imidazoles/pharmacology
MH  - Immune Tolerance/*immunology
MH  - MAP Kinase Signaling System/*drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred DBA
MH  - Pyridines/pharmacology
MH  - Receptors, Transforming Growth Factor beta/*antagonists & inhibitors
EDAT- 2012/09/14 06:00
MHDA- 2013/03/19 06:00
CRDT- 2012/09/14 06:00
PHST- 2012/02/22 00:00 [received]
PHST- 2012/09/04 00:00 [accepted]
PHST- 2012/09/14 06:00 [entrez]
PHST- 2012/09/14 06:00 [pubmed]
PHST- 2013/03/19 06:00 [medline]
AID - 10.1002/art.37702 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2013 Jan;65(1):120-9. doi: 10.1002/art.37702.