PMID- 16675346
OWN - NLM
STAT- MEDLINE
DCOM- 20060607
LR  - 20181201
IS  - 0091-6749 (Print)
IS  - 0091-6749 (Linking)
VI  - 117
IP  - 5
DP  - 2006 May
TI  - Toll-like receptor agonists differentially regulate cysteinyl-leukotriene 
      receptor 1 expression and function in human dendritic cells.
PG  - 1155-62
AB  - BACKGROUND: Dendritic cells (DCs) acquire, during their maturation, the 
      expression of the chemokine receptor CCR7 and the ability to migrate to lymph 
      nodes in response to CC chemokine ligand 19 (CCL19). This migration is impaired 
      in mice lacking the leukotriene (LT) C4 transporter and restored by addition of 
      exogenous LTC4. OBJECTIVE: To define the role of LT in human DC function, we 
      studied the expression and function of the cysteinyl-leukotriene (CysLT) 
      receptors during DC differentiation from monocytes and subsequent maturation. 
      METHODS: Receptor expression was measured by flow cytometry and real-time PCR. 
      Responsiveness to LTD4 stimulation was assessed by calcium flux and chemotaxis. 
      RESULTS: Maturation of DC with LPS, a classic Toll-like receptor 4 agonist, 
      reduced CysLT receptor 1 (CysLT1) expression by 50%, whereas CysLT receptor 2 
      expression was increased. In contrast, the Toll-like receptor 3 agonist poly 
      inosinic and cytidylic acid (polyI:C) had no effect on receptor expression. 
      Downregulation of CysLT1 expression by LPS could not be mimicked by TNF-alpha 
      alone or in combination with IL-1beta or IL-6. It was, however, prevented by 
      inhibitors of COX and could be reproduced by a combination of TNF-alpha and 
      prostaglandin E2. Immature DCs and DCs matured with polyI:C, but not with LPS, 
      responded to LTD4 with a robust cytosolic calcium flux, which was prevented by 
      the CysLT1 antagonist montelukast. LTD4 induced DC chemotaxis and enhanced DC 
      migration in response to CCL19 in DCs matured with polyI:C, but only weakly in 
      DCs matured with LPS. CONCLUSION: Our data suggest that human DCs may 
      differentially respond to leukotriene, depending on their maturational stimuli. 
      CLINICAL IMPLICATIONS: Our study demonstrates that some microbial agents can 
      reduce the migration of dendritic cells in response to leukotrienes, with 
      potential for differential involvement of these cells in allergic inflammation.
FAU - Thivierge, Maryse
AU  - Thivierge M
AD  - Immunology Division, Department of Pediatrics, Faculty of Medicine, Universite de 
      Sherbrooke, Quebec, Canada.
FAU - Stankova, Jana
AU  - Stankova J
FAU - Rola-Pleszczynski, Marek
AU  - Rola-Pleszczynski M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060221
PL  - United States
TA  - J Allergy Clin Immunol
JT  - The Journal of allergy and clinical immunology
JID - 1275002
RN  - 0 (Leukotrienes)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, Leukotriene)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (cysteinyl-leukotriene)
RN  - 2CU6TT9V48 (Leukotriene C4)
RN  - 73836-78-9 (Leukotriene D4)
RN  - K848JZ4886 (Cysteine)
RN  - LRF7RW46ID (leukotriene D4 receptor)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium/metabolism
MH  - Cells, Cultured
MH  - Chemotaxis, Leukocyte/immunology
MH  - Cysteine/physiology
MH  - Dendritic Cells/immunology/*metabolism
MH  - Humans
MH  - Leukotriene C4/biosynthesis/*physiology
MH  - Leukotriene D4/biosynthesis/*physiology
MH  - Leukotrienes/physiology
MH  - Membrane Proteins/*genetics/*metabolism
MH  - Receptors, Leukotriene/*genetics/*metabolism
MH  - Toll-Like Receptors/*agonists
EDAT- 2006/05/06 09:00
MHDA- 2006/06/08 09:00
CRDT- 2006/05/06 09:00
PHST- 2005/08/23 00:00 [received]
PHST- 2005/11/16 00:00 [revised]
PHST- 2005/12/20 00:00 [accepted]
PHST- 2006/05/06 09:00 [pubmed]
PHST- 2006/06/08 09:00 [medline]
PHST- 2006/05/06 09:00 [entrez]
AID - S0091-6749(06)00004-2 [pii]
AID - 10.1016/j.jaci.2005.12.1342 [doi]
PST - ppublish
SO  - J Allergy Clin Immunol. 2006 May;117(5):1155-62. doi: 
      10.1016/j.jaci.2005.12.1342. Epub 2006 Feb 21.