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H ê s § ´ Ë á ¯ á Z q- 3 - 9 ¬28 ã9Ô ã9Õ%Y2 ã"á 99æ00 - 109æ40 . 6 * Z f39æ ë , 9 P f 4 f f 9 # ] f é Ï(» ø î" " " ó é4P 3439æ5/ ! è = 5!¢9Ô z L "õ% $|

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Page 1: H ê s § ´ Ë á ¯ á Z q- 3 - 9 ¬28 ã9Ô ã9Õ%Y2 ã"á 99æ00 - 109æ40 . 6 * Z f39æ ë , 9 P f 4 f f 9 # ] f é Ï(» ø î" " " ó é4P 3439æ5/ ! è = 5!¢9Ô z L "õ% $|
Page 2: H ê s § ´ Ë á ¯ á Z q- 3 - 9 ¬28 ã9Ô ã9Õ%Y2 ã"á 99æ00 - 109æ40 . 6 * Z f39æ ë , 9 P f 4 f f 9 # ] f é Ï(» ø î" " " ó é4P 3439æ5/ ! è = 5!¢9Ô z L "õ% $|

- 1 -

820 9 27 13 00 17 00 18 00

9 28 9 00 13 00

1 3

060-8638 15 7

9 27 1

13 00 - 13 10

13 10 - 14 30 1

13 10 - 13 30 1Osteopontin promoter SNPs nt

-155

13 30 - 13 50 2

1) 2) 2) 3) 3) 3)

4) 4) 4) 5)

1) 2) 3) 4)

5)13 50 - 14 10 3

osteopontin1) 1) 1) 2) 3)

3) 3) 4) 1) 1)

1) 1) 1)

1) 2)

Department of Cenllular and Molecular Pathology, German Cancer Research

Center 3) 4)

14 10 - 14 30 4 HIV OPN

Haorile Y Chagan1) 1) 1) Shenwei Li1), 2)

3) 3) 1),2) 1)

1) 2) ( ) 3)

Page 3: H ê s § ´ Ë á ¯ á Z q- 3 - 9 ¬28 ã9Ô ã9Õ%Y2 ã"á 99æ00 - 109æ40 . 6 * Z f39æ ë , 9 P f 4 f f 9 # ] f é Ï(» ø î" " " ó é4P 3439æ5/ ! è = 5!¢9Ô z L "õ% $|

- 2 -

14 30 - 15 30 2

14 30 - 14 50 5

1) 1), 2) 1), 2) 3) 3)

3) 3) ) 3) 1)

1) 3)

2) 4)

14 50 - 15 10 6(OPN)

1) 1) 2) 3) 4) 4)

5) 1) 1) 1) 5)

4) Shau-Ku Huang2) 1)

1) 2) Johns Hopkins Asthma and Allergy Center, Baltimore, MD, USA 3)4) 5)

15 10 - 15 30 79

15 30 - 15 40

15 40 - 17 00

(Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School)

18 00 -

Page 4: H ê s § ´ Ë á ¯ á Z q- 3 - 9 ¬28 ã9Ô ã9Õ%Y2 ã"á 99æ00 - 109æ40 . 6 * Z f39æ ë , 9 P f 4 f f 9 # ] f é Ï(» ø î" " " ó é4P 3439æ5/ ! è = 5!¢9Ô z L "õ% $|

- 3 -

9 28 2

9 00 - 10 40 3

9 00 - 9 20 84 9

9 20 - 9 40 99

9 40 - 10 00 10

1) 1) 1) 1) 2)

2) Susan R. Rittling3), David T. Denhardt3), 1)

1) 2)

3) Departments of Genetics and Cell Biology and Neuroscience,

Rutgers University, Piscataway, NJ, USA.

10 00 - 10 20 11

1) 2) 2) 2) 2)

2) 1)

1) 2)

10 20 - 10 40 129

1) 1) 1) 1) 2) 1)

1) 2)

10 40 - 10 50

10 50 - 11 50

10 50 - 11 10 13

1) 2) 1) 1),3) 2)

1)

1) 2) 3)

Page 5: H ê s § ´ Ë á ¯ á Z q- 3 - 9 ¬28 ã9Ô ã9Õ%Y2 ã"á 99æ00 - 109æ40 . 6 * Z f39æ ë , 9 P f 4 f f 9 # ] f é Ï(» ø î" " " ó é4P 3439æ5/ ! è = 5!¢9Ô z L "õ% $|

- 4 -

11 10 - 11 30 14

1) 2) 3) 2) 3)

4) 4)

1) 2)

3) 4)

11 30 - 11 50 15 Osteopontin is dispensable for protection against high load systemic

fungal infection Ikuko Sato1), Nobuchika Yamamoto2), Susan R. Rittling5), David T. Denhardt5),

Motohiro Hino3), Junko Morimoro6), Fumihiko Sakai4), Akihiko Fujie1), and

Toshimitsu Uede6)

1) 2)

3) 4) 5) Rutgers University, Nelson

Laboratories 6)

11 50 - 12 00

Page 6: H ê s § ´ Ë á ¯ á Z q- 3 - 9 ¬28 ã9Ô ã9Õ%Y2 ã"á 99æ00 - 109æ40 . 6 * Z f39æ ë , 9 P f 4 f f 9 # ] f é Ï(» ø î" " " ó é4P 3439æ5/ ! è = 5!¢9Ô z L "õ% $|

- 5 -

1

Osteopontin promoter SNPs nt -155

CTh1 osteopontin cytokine

osteopontin

osteopontin promoter 100 nt-155, -616, -1,748 3SNPs nt -443 SNP HepG2

promoter assay nt -155, nt -443 SNPs nt -155 deletion mutation allele G PCnt -155 Y SRY HNF-3/fkh homolog HFH FoxD3

HepG2 gel-shift assaynt -155 deletion mutation oligonucleoside SRY, FoxD3

allele G SRY Heladeletion mutation FoxD3

osteopontin nt -155 alleleSNPs

Memo

Page 7: H ê s § ´ Ë á ¯ á Z q- 3 - 9 ¬28 ã9Ô ã9Õ%Y2 ã"á 99æ00 - 109æ40 . 6 * Z f39æ ë , 9 P f 4 f f 9 # ] f é Ï(» ø î" " " ó é4P 3439æ5/ ! è = 5!¢9Ô z L "õ% $|

- 6 -

2

1) 2) 2) 3) 3) 3) 4)

4) 4) 5)

1) 2) 3) 4) 5)

viable

(OPN)

OPN OPN G-156Del

(DCM) 120(%FS)

%FS 5% DCM 80OPN, ANP OPN G-156Del

PCR-RFLP OPN ANP(p<0.00001) OPN G156 (

%; Del/Del 37%, Del/G + G/G 67%, p=0.006)OPN

OPN G-156Del

Memo

Page 8: H ê s § ´ Ë á ¯ á Z q- 3 - 9 ¬28 ã9Ô ã9Õ%Y2 ã"á 99æ00 - 109æ40 . 6 * Z f39æ ë , 9 P f 4 f f 9 # ] f é Ï(» ø î" " " ó é4P 3439æ5/ ! è = 5!¢9Ô z L "õ% $|

- 7 -

3

osteopontin

1) 1) 1) 2) 3) 3) 3)

4) 1) 1) 1) 1) 1)

1) 2) Department of Cenllular and Molecular Pathology, German Cancer Research Center 3)4)

OPNII

OPN OPN(OPN N-half)

OPN (OPN-Full) OPN N-half

2008 2 615 OPN-Full OPN N-half CRP IL-6

( ) ( )

71.3 4.8 14 OPN-Full 557157 810 267 ng/ml p<0.001 OPN N-half CRP IL-6

( 0.246 0.151, 0.210 0.121 mg/dl, p=0.073, IL-6 3.00 4.10, 3.00 1.61 pg/ml, p>0.999) OPN

(LSL LB-4225, C OPN-N (IBL 11108)

OPN-FullN-half

Memo

Page 9: H ê s § ´ Ë á ¯ á Z q- 3 - 9 ¬28 ã9Ô ã9Õ%Y2 ã"á 99æ00 - 109æ40 . 6 * Z f39æ ë , 9 P f 4 f f 9 # ] f é Ï(» ø î" " " ó é4P 3439æ5/ ! è = 5!¢9Ô z L "õ% $|

- 8 -

4

HIV OPN

Haorile Y Chagan1) 1) 1) Shenwei Li1), 2) 3) 3)

1),2) 1)

1) 2) ( ) 3)

HIV CD4HAART

(IRS)HAART proinflammatory cytokine OPN

HAARTOPN

OPN - (GAL-9)HIV/ B (HBV) HIV(PCP) (MTB) (KS)

HAART 3 HAART80

HIVOPN GAL-9 PCP

OPN PCP GAL-9HAART GAL-9

OPN IRSHAART OPN

HAART

Memo

Page 10: H ê s § ´ Ë á ¯ á Z q- 3 - 9 ¬28 ã9Ô ã9Õ%Y2 ã"á 99æ00 - 109æ40 . 6 * Z f39æ ë , 9 P f 4 f f 9 # ] f é Ï(» ø î" " " ó é4P 3439æ5/ ! è = 5!¢9Ô z L "õ% $|

- 9 -

5

1) 1), 2) 1), 2) 3) 3) 3)

3) ) 3) 1)

1) 3)2) 4)

OPN (EAU)(C57BL/6; B6) EAU OPN

RNA OPN

B6 (hIRBP1-20:GPTHLFQPSLVLDMAKVLLD) 200 g

0.1 g EAU OPN (M )400 g/ IgG RNA

OPN siRNA (OPN-siRNA) siRNA (control-siRNA 50 g/ (1 ml PBS) hydrodynamichIRBP1-20 3H-thymidineELISA

M5 EAU B6M5 T

IFN- TNF- OPN siRNA M5

IFN- TNF- OPN-siRNAEAU T

Memo

Page 11: H ê s § ´ Ë á ¯ á Z q- 3 - 9 ¬28 ã9Ô ã9Õ%Y2 ã"á 99æ00 - 109æ40 . 6 * Z f39æ ë , 9 P f 4 f f 9 # ] f é Ï(» ø î" " " ó é4P 3439æ5/ ! è = 5!¢9Ô z L "õ% $|

- 10 -

6

(OPN)

1) 1) 2) 3) 4) 4) 5)

1) 1) 1) 5) 4) Shau-Ku Huang2)

1)

1) 2) Johns Hopkins Asthma and Allergy Center, Baltimore, MD, USA 3) 4)

5)

OPN Th1Th2

OPN

OPNOPN OPN

OPN (2K1) -4 (P1H4)OPN (M5)

OPN (p 0.005)(r=0.530,p 0.01) OPN (p 0.01) 2K1

P1H4 (p 0.01) M5 BAL(p 0.05)

OPN

Memo

Page 12: H ê s § ´ Ë á ¯ á Z q- 3 - 9 ¬28 ã9Ô ã9Õ%Y2 ã"á 99æ00 - 109æ40 . 6 * Z f39æ ë , 9 P f 4 f f 9 # ] f é Ï(» ø î" " " ó é4P 3439æ5/ ! è = 5!¢9Ô z L "õ% $|

7

9

(RA)(OPN)

9 1 9

9 (55A2C)9

RA CAIA ( ) CAIA9 mRNA

FACS (FLS) 9FLS 9 (OPN, -C)9 FLS IL-6, IL-1

mRNA CAIA55A2C 9 in vivo

( )55A2C IL-6, IL-1

9 FLS9 RA

Memo

Page 13: H ê s § ´ Ë á ¯ á Z q- 3 - 9 ¬28 ã9Ô ã9Õ%Y2 ã"á 99æ00 - 109æ40 . 6 * Z f39æ ë , 9 P f 4 f f 9 # ] f é Ï(» ø î" " " ó é4P 3439æ5/ ! è = 5!¢9Ô z L "õ% $|

- 12 -

Harvey Cantor Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, U. S. A.

(OPN)OPN

(DC)OPN OPN OPN

AUG AUG

OPN OPN (plasmacytoid DC/pDC) TLR9 IRF-7

IFN (conventional DC/cDC) OPN IL-27IL-17 (Th17)

OPN in vivo pDC OPN IFNcDC OPN Th17

(EAE) OPN

Memo

Page 14: H ê s § ´ Ë á ¯ á Z q- 3 - 9 ¬28 ã9Ô ã9Õ%Y2 ã"á 99æ00 - 109æ40 . 6 * Z f39æ ë , 9 P f 4 f f 9 # ] f é Ï(» ø î" " " ó é4P 3439æ5/ ! è = 5!¢9Ô z L "õ% $|

- 13 -

8

4 9

(OPN) 4 9Ser162-Val-Val-Tyr-Gly-Leu-Arg168(SVVYGLR) OPN

(MMP) -3,-7 Arg168/Ser169 Gly166/Leu167SVVYGLR 4

Leu167 9 Tyr165OPN SVVYGLR 4 9

SVVYGLR Alanine4 9

Val164 Tyr165 Leu167 4 9Arg168 9

9 OPNMMP OPN N 4 9

Arg168 9Arg168 (R168A) 4 9

Arg168 4 9

Memo

Page 15: H ê s § ´ Ë á ¯ á Z q- 3 - 9 ¬28 ã9Ô ã9Õ%Y2 ã"á 99æ00 - 109æ40 . 6 * Z f39æ ë , 9 P f 4 f f 9 # ] f é Ï(» ø î" " " ó é4P 3439æ5/ ! è = 5!¢9Ô z L "õ% $|

- 14 -

9

9

(APC)

APC APC9

92 9

TGF T9 IL-12p40 T

T

Memo

Page 16: H ê s § ´ Ë á ¯ á Z q- 3 - 9 ¬28 ã9Ô ã9Õ%Y2 ã"á 99æ00 - 109æ40 . 6 * Z f39æ ë , 9 P f 4 f f 9 # ] f é Ï(» ø î" " " ó é4P 3439æ5/ ! è = 5!¢9Ô z L "õ% $|

- 15 -

10

1) 1) 1) 1) 2) 2) Susan R. Rittling3),David T. Denhardt3), 1)

1) 2)3) Departments of Genetics and Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, USA.

(OPN)hUVEC in vitro OPN

in vivo OPNhUVEC SVVYGLR

OPN OPN( KO ) (n = 32) ( WT ) (n = 32)

3 7 14Platelet/endothelial cell adhesion molecule-1

(PECAM-1)

SVVYGLROPN

PECAM-1 KOWT (0.164 (+/-0.096) mm WT 0.478 (+/-0.193) mm)

SVVYGLR OPNOPN OPN

Memo

Page 17: H ê s § ´ Ë á ¯ á Z q- 3 - 9 ¬28 ã9Ô ã9Õ%Y2 ã"á 99æ00 - 109æ40 . 6 * Z f39æ ë , 9 P f 4 f f 9 # ] f é Ï(» ø î" " " ó é4P 3439æ5/ ! è = 5!¢9Ô z L "õ% $|

- 16 -

11

1) 2) 2) 2) 2) 2)

1)

1) 2)

(KO ) (WT )

5mm

F4/80 SMA

3 6 8 10 12 KOKO 6 8

3 6 8 KO WTKO WT F4/80 SMA

Memo

Page 18: H ê s § ´ Ë á ¯ á Z q- 3 - 9 ¬28 ã9Ô ã9Õ%Y2 ã"á 99æ00 - 109æ40 . 6 * Z f39æ ë , 9 P f 4 f f 9 # ] f é Ï(» ø î" " " ó é4P 3439æ5/ ! è = 5!¢9Ô z L "õ% $|

- 17 -

12

9

1) 1) 1) 1) 2) 1)

1) 2)

3 1, 5 1, 6 49 1

9 (55A2C) 9

9-C in vivo 9

(NHG) 55A2C

55A2C CD3155A2C CD31

55A2C 55A2C

in vitro 955A2C

9

Memo

Page 19: H ê s § ´ Ë á ¯ á Z q- 3 - 9 ¬28 ã9Ô ã9Õ%Y2 ã"á 99æ00 - 109æ40 . 6 * Z f39æ ë , 9 P f 4 f f 9 # ] f é Ï(» ø î" " " ó é4P 3439æ5/ ! è = 5!¢9Ô z L "õ% $|

- 18 -

13

1) 2) 1) 1),3) 2) 1)

1) 2) 3)

IL-1, IL-6 TNF-

(OPN)(A/PR/8 (H1N1))

(A/Aichi/2/68(H3N2)) OPNOPN A/PR/8

A/Aichi/2/68 OPNA/Aichi/2/68

A/PR/8 OPNOPN A/PR/8

OPNOPN in vitro

OPNOPN

OPN

Memo

Page 20: H ê s § ´ Ë á ¯ á Z q- 3 - 9 ¬28 ã9Ô ã9Õ%Y2 ã"á 99æ00 - 109æ40 . 6 * Z f39æ ë , 9 P f 4 f f 9 # ] f é Ï(» ø î" " " ó é4P 3439æ5/ ! è = 5!¢9Ô z L "õ% $|

- 19 -

14

1) 2) 3) 2) 3) 4) 4)

1) 2) 3)4)

(interstitium)

(OPN)OPN

OPN OPNOPN

(KO ) (WT C57BL/6J wild type)OPN

(C57BL/6J ) (O ) (C )8 11 12 sacrifice

OPN ( ) WTKO (mg)(mm2) ( m) WT KO 1/2

KO OPN( ) C O

C O 1/3 1/3O C 1/2

OPN OPNOPN OPN

OPN OPN

Memo

Page 21: H ê s § ´ Ë á ¯ á Z q- 3 - 9 ¬28 ã9Ô ã9Õ%Y2 ã"á 99æ00 - 109æ40 . 6 * Z f39æ ë , 9 P f 4 f f 9 # ] f é Ï(» ø î" " " ó é4P 3439æ5/ ! è = 5!¢9Ô z L "õ% $|

- 20 -

15

Osteopontin is dispensable for protection against high load systemic fungal infection

Ikuko Sato1), Nobuchika Yamamoto2), Susan R. Rittling5), David T. Denhardt5), Motohiro Hino3), Junko Morimoro6), Fumihiko Sakai4), Akihiko Fujie1), and Toshimitsu Uede6)

1) 2) 3) 4) 5) Rutgers University, Nelson Laboratories 6)

RGDSLAYGLR

M5 J Clin Invest. 2003;112(2):181-8. M5

Antimicrob Agents Chemother. 2005 49(7):3053-5.

M5

Memo

Page 22: H ê s § ´ Ë á ¯ á Z q- 3 - 9 ¬28 ã9Ô ã9Õ%Y2 ã"á 99æ00 - 109æ40 . 6 * Z f39æ ë , 9 P f 4 f f 9 # ] f é Ï(» ø î" " " ó é4P 3439æ5/ ! è = 5!¢9Ô z L "õ% $|

370-0831 5 1TEL: 027-310-8040 FAX 027-310-8045

[email protected]