PMID- 18059372
OWN - NLM
STAT- MEDLINE
DCOM- 20080703
LR  - 20170120
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Linking)
VI  - 16
IP  - 2
DP  - 2008 Feb
TI  - Downregulation of monocyte chemoattractant protein-1 involving short interfering 
      RNA attenuates hapten-induced contact hypersensitivity.
PG  - 387-95
AB  - Contact hypersensitivity (CHS) is a common skin disease, presenting clinically as 
      allergic contact dermatitis. At inflammatory sites in a typical CHS model in the 
      mouse ear, elevated expression of monocyte chemoattractant protein-1 (MCP-1) has 
      been reported. MCP-1 is a potent chemotactic factor for many types of leukocytes 
      including monocytes/macrophages and T cells. In this study, we aimed at 
      developing a therapy for CHS involving RNA interference targeting MCP-1. A short 
      interfering RNA (siRNA) to mouse MCP-1 successfully inhibited the secretion of 
      MCP-1 by a fibroblastic cell line, L929, and RAW 264.7 cells derived from 
      macrophages, and strikingly suppressed ear swelling in a CHS model. The siRNA 
      systemically administered inhibited the infiltration of both 
      monocytes/macrophages and T cells in the CHS model. Atelocollagen was used in 
      this therapy as a delivery reagent for siRNA into the animal body. Atelocollagen 
      facilitated the incorporation of the siRNA into macrophages/monocytes and 
      fibroblasts, which vigorously secrete MCP-1 protein at inflammatory sites in CHS. 
      This therapy had no adverse effects such as induction of interferon, or liver or 
      renal damage. Our data indicate that the systemic delivery of siRNA targeting 
      MCP-1 is a potent therapeutic strategy for CHS treatment.
FAU - Ishimoto, Takuji
AU  - Ishimoto T
AD  - Department of Biochemistry, Nagoya University Graduate School of Medicine, 
      Nagoya, Japan.
FAU - Takei, Yoshifumi
AU  - Takei Y
FAU - Yuzawa, Yukio
AU  - Yuzawa Y
FAU - Hanai, Koji
AU  - Hanai K
FAU - Nagahara, Shunji
AU  - Nagahara S
FAU - Tarumi, Yuzo
AU  - Tarumi Y
FAU - Matsuo, Seiichi
AU  - Matsuo S
FAU - Kadomatsu, Kenji
AU  - Kadomatsu K
LA  - eng
PT  - Journal Article
DEP - 20071204
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Haptens)
RN  - 0 (Liposomes)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (atelocollagen)
RN  - 9007-34-5 (Collagen)
RN  - D241E059U6 (Dinitrofluorobenzene)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cells, Cultured
MH  - Chemokine CCL2/*genetics/metabolism
MH  - Collagen/metabolism
MH  - Dermatitis, Contact/etiology/genetics/*therapy
MH  - Dinitrofluorobenzene
MH  - Ear/pathology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Haptens
MH  - Immunohistochemistry
MH  - Inflammation/chemically induced/genetics/therapy
MH  - Liposomes/chemistry
MH  - Macrophages/immunology/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - *RNA Interference
MH  - RNA, Small Interfering/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocytes/immunology/metabolism
MH  - Transfection
EDAT- 2007/12/07 09:00
MHDA- 2008/07/04 09:00
CRDT- 2007/12/07 09:00
PHST- 2007/12/07 09:00 [pubmed]
PHST- 2008/07/04 09:00 [medline]
PHST- 2007/12/07 09:00 [entrez]
AID - S1525-0016(16)31406-X [pii]
AID - 10.1038/sj.mt.6300360 [doi]
PST - ppublish
SO  - Mol Ther. 2008 Feb;16(2):387-95. doi: 10.1038/sj.mt.6300360. Epub 2007 Dec 4.