PMID- 23075496
OWN - NLM
STAT- MEDLINE
DCOM- 20130419
LR  - 20211203
IS  - 1423-0097 (Electronic)
IS  - 1018-2438 (Linking)
VI  - 160
IP  - 3
DP  - 2013
TI  - Inhibition of histamine H1 receptor activity modulates proinflammatory cytokine 
      production of dendritic cells through c-Rel activity.
PG  - 265-74
LID - 10.1159/000341637 [doi]
AB  - BACKGROUND: Histamine exerts diverse effects on immune regulation through four 
      types of histamine receptors (HRs). Among them, type 1 receptor (H1R) plays an 
      important role in allergic inflammation. Dendritic cells (DCs), which express at 
      least three types of HRs, are professional antigen-presenting cells controlling 
      the development of allergic inflammation. However, the molecular mechanisms 
      involved in H1R-mediated NF-kB signaling of DCs remain poorly defined. METHODS: 
      Bone-marrow (BM)-derived DCs (BM-DCs) were treated with H1R inverse agonists to 
      interrupt basal H1R-mediated signaling. The crosstalk of H1R-mediated signaling 
      and the NF-kB pathway was examined by NF-kB cellular activity using a luciferase 
      reporter assay, NF-kB subunit analysis using Western blotting and TNF-alpha promoter 
      activity using chromatin immunoprecipitation. RESULTS: Blockage of H1R signaling 
      by inverse agonists significantly inhibited TNF-alpha and IL-6 production of BM-DCs. 
      H1R-specific agonists were able to enhance TNF-alpha production, but this 
      overexpression was significantly inhibited by NF-kB inhibitor. The H1R inverse 
      agonist ketotifen also suppressed cellular NF-kB activity, suggesting crosstalk 
      between H1R and NF-kB signaling in DCs. After comprehensive analysis of NF-kB 
      subunits, c-Rel protein expression was significantly down-regulated in 
      ketotifen-treated BM-DCs, which led to inhibition of the promoter activity of 
      TNF-alpha. Finally, adoptive transfer of the ketotifen-treated BM-DCs did not induce 
      significant allergic airway inflammation compared to that of control cells in 
      vivo. CONCLUSIONS: Our results suggest that c-Rel controls H1R-mediated 
      proinflammatory cytokine production in DCs. This study provides a potential 
      mechanism of H1R-mediated signaling and NF-kB pathway crosstalk in allergic 
      inflammation.
CI  - Copyright (c) 2012 S. Karger AG, Basel.
FAU - Lee, Chin-Lai
AU  - Lee CL
AD  - Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical 
      University, Kaohsiung, Taiwan, ROC.
FAU - Hsu, Shih-Hsien
AU  - Hsu SH
FAU - Jong, Yuh-Jyh
AU  - Jong YJ
FAU - Hung, Chih-Hsing
AU  - Hung CH
FAU - Suen, Jau-Ling
AU  - Suen JL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121017
PL  - Switzerland
TA  - Int Arch Allergy Immunol
JT  - International archives of allergy and immunology
JID - 9211652
RN  - 0 (Histamine Agonists)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (Proto-Oncogene Proteins c-rel)
RN  - 0 (Receptors, Histamine H1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - X49220T18G (Ketotifen)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - Dendritic Cells/drug effects/*immunology
MH  - Drug Inverse Agonism
MH  - Female
MH  - Gene Expression Regulation/drug effects/immunology
MH  - Histamine Agonists/pharmacology
MH  - Hypersensitivity/drug therapy/*immunology
MH  - Immunosuppression Therapy
MH  - Inflammation Mediators/immunology/metabolism
MH  - Interleukin-6/genetics/metabolism
MH  - Ketotifen/pharmacology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - NF-kappa B/immunology/*metabolism
MH  - Proto-Oncogene Proteins c-rel/genetics/*metabolism
MH  - Receptor Cross-Talk/drug effects/immunology
MH  - Receptors, Histamine H1/immunology/*metabolism
MH  - Signal Transduction/drug effects/immunology
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism
EDAT- 2012/10/19 06:00
MHDA- 2013/04/23 06:00
CRDT- 2012/10/19 06:00
PHST- 2012/01/08 00:00 [received]
PHST- 2012/07/06 00:00 [accepted]
PHST- 2012/10/19 06:00 [entrez]
PHST- 2012/10/19 06:00 [pubmed]
PHST- 2013/04/23 06:00 [medline]
AID - 000341637 [pii]
AID - 10.1159/000341637 [doi]
PST - ppublish
SO  - Int Arch Allergy Immunol. 2013;160(3):265-74. doi: 10.1159/000341637. Epub 2012 
      Oct 17.