PMID- 18798077
OWN - NLM
STAT- MEDLINE
DCOM- 20081104
LR  - 20191210
IS  - 1460-2202 (Electronic)
IS  - 0271-3683 (Linking)
VI  - 33
IP  - 9
DP  - 2008 Sep
TI  - Pathogenesis of herpetic stromal keratitis in CCR5- and/or CXCR3-deficient mice.
PG  - 736-49
LID - 10.1080/02713680802344716 [doi]
AB  - PURPOSE: Herpetic stromal keratitis (HSK) is an immunopathological reaction to 
      herpes simplex virus type 1 (HSV-1) corneal infection. It has been reported that 
      CD4+ cells play the most important role in the pathogenesis of this disease. In 
      this study, we have focused on two chemokine receptors, CCR5 and CXCR3, which are 
      expressed on CD4+ Th1 cells in mice HSK model. METHODS: CCR5-deficient (CCR5KO), 
      CXCR3-deficient (CXCR3KO), CCR5/CXCR3 double-deficient (DKO), and wild type (WT) 
      mice (C57/BL6 background) were infected intracorneally with HSV-1 (CHR3 strain). 
      The corneas were examined biomicroscopically, and cryosections of the corneas 
      were examined histologically and immunohistochemically. Real-time RT-PCR and 
      RNase protection assay (RPA) were performed, and the virus titers were measured 
      in excised eyes and trigeminal ganglia (TG). RESULTS: The HSK clinical severity 
      in DKO mice was significantly lower than that in WT mice, and this was reversed 
      by transfer of cells from the spleen of WT mice to DKO mice. Histologically, the 
      numbers of T cells (CD4+ and CD8+ cells) and neutrophils infiltrating the cornea 
      were significantly fewer in CCR5KO, CXCR3KO, and DKO mice. Transcript levels of 
      immune-related cell surface marker in the eye by RPA were reduced in DKO mice. 
      The expression of I-TAC was significantly increased in the cornea of CCR5KO mice, 
      and MIP-1alpha and MIP-1beta were significantly lower in CXCR3KO mice than in WT 
      mice by RT-PCR. There were no significant differences of virus titers in the eye 
      and TG among any groups of mice except the increase in the TG of DKO mice on day 
      5 PI. CONCLUSIONS: The suppression of chemotaxis and activation of CD4+ Th1 cells 
      by the lacking of CXCR3 and CCR5 causes a decrease of other infiltrating cells, 
      resulting in a lower severity of HSK. These results suggest that targeting 
      chemokine receptors is a promising way to treat HSK.
FAU - Komatsu, Keiko
AU  - Komatsu K
AD  - Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori 
      University, Tottori, Japan.
FAU - Miyazaki, Dai
AU  - Miyazaki D
FAU - Morohoshi, Kei
AU  - Morohoshi K
FAU - Kuo, Chuan-Hui
AU  - Kuo CH
FAU - Kakimaru-Hasegawa, Akiko
AU  - Kakimaru-Hasegawa A
FAU - Komatsu, Naoki
AU  - Komatsu N
FAU - Namba, Sachiko
AU  - Namba S
FAU - Haino, Makoto
AU  - Haino M
FAU - Matsushima, Kouji
AU  - Matsushima K
FAU - Inoue, Yoshitsugu
AU  - Inoue Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Curr Eye Res
JT  - Current eye research
JID - 8104312
RN  - 0 (Ccl3 protein, mouse)
RN  - 0 (Ccl4 protein, mouse)
RN  - 0 (Chemokine CCL3)
RN  - 0 (Chemokine CCL4)
RN  - 0 (Chemokine CXCL11)
RN  - 0 (Cxcl11 protein, mouse)
RN  - 0 (Cxcr3 protein, mouse)
RN  - 0 (DNA, Viral)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR5)
RN  - 0 (Receptors, CXCR3)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Chemokine CCL3/genetics/metabolism
MH  - Chemokine CCL4/genetics/metabolism
MH  - Chemokine CXCL11/genetics/metabolism
MH  - Chlorocebus aethiops
MH  - Corneal Stroma/innervation/metabolism/*virology
MH  - DNA, Viral/genetics
MH  - Gene Dosage
MH  - Herpesvirus 1, Human/physiology
MH  - Immunoenzyme Techniques
MH  - Keratitis, Herpetic/*etiology/genetics/immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neutrophils/immunology
MH  - RNA, Messenger/metabolism
MH  - Receptors, CCR5/*deficiency/physiology
MH  - Receptors, CXCR3/*deficiency/physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Trigeminal Ganglion/virology
MH  - Vero Cells/virology
EDAT- 2008/09/18 09:00
MHDA- 2008/11/05 09:00
CRDT- 2008/09/18 09:00
PHST- 2008/09/18 09:00 [pubmed]
PHST- 2008/11/05 09:00 [medline]
PHST- 2008/09/18 09:00 [entrez]
AID - 902507468 [pii]
AID - 10.1080/02713680802344716 [doi]
PST - ppublish
SO  - Curr Eye Res. 2008 Sep;33(9):736-49. doi: 10.1080/02713680802344716.