PMID- 19175598
OWN - NLM
STAT- MEDLINE
DCOM- 20090526
LR  - 20171116
IS  - 1398-9995 (Electronic)
IS  - 0105-4538 (Linking)
VI  - 64
IP  - 3
DP  - 2009 Mar
TI  - Inhibition of allergic responses by CD40 gene silencing.
PG  - 387-97
LID - 10.1111/j.1398-9995.2008.01839.x [doi]
AB  - BACKGROUND: Gene silencing using small interfering RNA (siRNA) is a potent method 
      of specifically knocking down molecular targets. Small interfering RNA is 
      therapeutically promising, however, treatment of allergic diseases with siRNA has 
      not been explored in vivo. The aim of this study was to evaluate therapeutic 
      effects of CD40 siRNA on inhibition of allergic responses. METHODS: Mice 
      sensitized with ovalbumin (OVA) and alum were treated with CD40 siRNA, scrambled 
      siRNA, or phosphate buffer saline (PBS) alone, and then challenged intranasally 
      with OVA. RESULTS: A significant reduction in nasal allergic symptoms was 
      observed in the CD40 siRNA treated OVA-allergic mice compared to the controls of 
      scrambled siRNA and PBS alone, which is correlated with the decrease of local 
      eosinophil accumulation. CD40 siRNA treatment knocked down CD40 expression on 
      dendritic cells (DCs) in vivo and impaired their antigen presenting function. 
      Treatment with CD40 siRNA resulted in inhibition of OVA-specific T cell response 
      and decrease of interleukin-4 (IL-4), IL-5, and interferon-gamma production from 
      T cells stimulated with OVA. Administration of CD40 siRNA also suppressed CD40 
      expression on B cells, resulting in down-regulation of OVA-specific 
      immunoglobulin E (IgE), IgG1, and IgG2a levels. Additionally, increased 
      regulatory T cells were observed in the CD40 siRNA treated mice. CONCLUSIONS: The 
      present study demonstrates a novel therapeutic use for siRNA in allergy. CD40 
      siRNA attenuated allergy through inhibition of DC and B cell functions and 
      generation of regulatory T (Treg) cells.
FAU - Suzuki, M
AU  - Suzuki M
AD  - Department of Surgery, University of Western Ontario, London, ON, Canada.
FAU - Zheng, X
AU  - Zheng X
FAU - Zhang, X
AU  - Zhang X
FAU - Ichim, T E
AU  - Ichim TE
FAU - Sun, H
AU  - Sun H
FAU - Kubo, N
AU  - Kubo N
FAU - Beduhn, M
AU  - Beduhn M
FAU - Shunnar, A
AU  - Shunnar A
FAU - Garcia, B
AU  - Garcia B
FAU - Min, W-P
AU  - Min WP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090128
PL  - Denmark
TA  - Allergy
JT  - Allergy
JID - 7804028
RN  - 0 (Allergens)
RN  - 0 (CD40 Antigens)
RN  - 0 (Immunoglobulin G)
RN  - 0 (RNA, Small Interfering)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Allergens/immunology
MH  - Animals
MH  - B-Lymphocytes/immunology
MH  - CD40 Antigens/*genetics/*immunology
MH  - Dendritic Cells/immunology
MH  - *Gene Silencing
MH  - Hypersensitivity/*genetics
MH  - Immunoglobulin E/blood/immunology
MH  - Immunoglobulin G/blood/immunology
MH  - Lymphocyte Activation/immunology
MH  - Lymphocyte Culture Test, Mixed
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Ovalbumin/immunology
MH  - RNA, Small Interfering
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocytes, Regulatory/immunology
EDAT- 2009/01/30 09:00
MHDA- 2009/05/27 09:00
CRDT- 2009/01/30 09:00
PHST- 2009/01/30 09:00 [entrez]
PHST- 2009/01/30 09:00 [pubmed]
PHST- 2009/05/27 09:00 [medline]
AID - ALL1839 [pii]
AID - 10.1111/j.1398-9995.2008.01839.x [doi]
PST - ppublish
SO  - Allergy. 2009 Mar;64(3):387-97. doi: 10.1111/j.1398-9995.2008.01839.x. Epub 2009 
      Jan 28.