ライフサイエンスコーパス: DPPI

1 DPPI and granule-associated serine proteases have been s

2 DPPI deletion reduced secretion by 20% and fluid myelope

3 DPPI inhibition during the second to fourth days of 5-da

4 DPPI therefore plays an essential role in the in vivo pr

5 us-induced asthma phenotype as a result of a DPPI-dependent neutrophil recruitment and cytokine respo

6 Although DPPI(-/-) mice have normal in vitro neutrophil chemotaxi

7 derived mast cells (BMMCs) from DPPI +/+ and DPPI -/- mice.

8 's role in sepsis, we compared DPPI(-/-) and DPPI(+/+) mice using the cecal ligation and puncture (CL

9 rom WT, CII-immunized mice into naive WT and DPPI(-/-) mice led to development of arthritis in WT mic

10 Wild-type (WT) and DPPI-deficient (DPPI(-/-)) mice backcrossed to DBA/1J mi

11 This study assesses DPPI mRNA and enzyme expression during T lymphocyte onto

12 Both DPPI mRNA and granzyme A mRNA expression in CD8+ T cells

13 However, peak levels of both DPPI and granzyme A expression were observed later in th

14 These results indicate that mast cell DPPI harms the septic host and that DPPI is a novel pote

15 Outcomes of CLP in mice lacking mast cell DPPI reveal that the absence of DPPI in mast cells, rath

16 When T cell DPPI activity was inhibited by >95% throughout 5-day MLC

17 identify an intracellular role for mast cell-DPPI (MC-DPPI) by activating prochymase and protryptase

18 o examine DPPI's role in sepsis, we compared DPPI(-/-) and DPPI(+/+) mice using the cecal ligation an

19 hemical staining of mouse incisors confirmed DPPI expression by ameloblasts.

20 h granzyme A mRNA is detected; consequently, DPPI appears to be available for the processing and acti

21 Wild-type (WT) and DPPI-deficient (DPPI(-/-)) mice backcrossed to DBA/1J mice for 10 genera

22 substrate, dipalmitoylphosphatidylinositol (DPPI).

23 In this study, we sought to examine DPPI expression in mouse enamel organ and determine if D

24 To examine DPPI's role in sepsis, we compared DPPI(-/-) and DPPI(+/

25 e to be the richest source yet described for DPPI, purifying up to 200 microg of enzyme per g of cell

26 bone marrow-derived mast cells (BMMCs) from DPPI +/+ and DPPI -/- mice.

27 show that cytotoxic lymphocytes derived from DPPI-/- mice contain normal amounts of granzymes A and B

28 Examination of mature enamel from DPPI null mice by FTIR showed no significant accumulatio

29 deduced sequence with that of rat and human DPPI revealed 90.1% and 77.8% identity, respectively.

30 d sequence is 86% identical to that of human DPPI.

31 vity of MMP20, KLK4, dipeptidyl peptidase I (DPPI) (an in vitro activator of KLK4), or cathepsin K.

32 he cysteine protease dipeptidyl peptidase I (DPPI) activates granule-associated serine proteases, sev

33 a mouse deficient in dipeptidyl peptidase I (DPPI) and established that DPPI is required for the full

34 Dipeptidyl peptidase I (DPPI) is a cysteine aminopeptidase that can activate sev

35 Dipeptidyl peptidase I (DPPI) is a cysteine protease found predominantly in myel

36 Dipeptidyl peptidase I (DPPI) is a cysteine protease required for the activation

37 Dipeptidyl peptidase I (DPPI) is a granule protease that plays a requisite role

38 Dipeptidyl peptidase I (DPPI) is a lysosomal cysteine protease critical for the

39 Dipeptidyl peptidase I (DPPI) is a lysosomal cysteine protease that catalyzes th

40 Dipeptidyl peptidase I (DPPI) is a lysosomal cysteine protease that has been imp

41 Dipeptidyl peptidase I (DPPI) is the sole activator in vivo of several granule-a

42 l loops in PAR(2) or dipeptidyl peptidase I (DPPI) knockout mice or in wild-type mice pretreated with

43 press high levels of dipeptidyl peptidase I (DPPI), a granule thiol protease able to convert the zymo

44 that the absence of dipeptidyl peptidase I (DPPI), a lysosomal cysteine protease found in neutrophil

45 protease cathepsin C/dipeptidyl peptidase I (DPPI).

46 ssion in mouse enamel organ and determine if DPPI could activate KLK4.

47 These results implicate DPPI and polymorphonuclear neutrophil-derived serine pro

48 st, the level of active tryptase (mMCP-6) in DPPI -/- BMMCs is 25% that of DPPI +/- BMMCs.

49 ficient to restore susceptibility to AAAs in DPPI-deficient mice, as well as aortic wall expression o

50 Although mice deficient in DPPI have defects in serine protease activation in multi

51 -6 is highly and differentially expressed in DPPI(-/-) mice compared with DPPI(+/+) mice.

52 Remarkably, deleting IL-6 expression in DPPI(-/-) mice eliminates the survival advantage.

53 hat mice with a loss-of-function mutation in DPPI are resistant to the development of elastase-induce

54 velopment of arthritis in WT mice but not in DPPI(-/-) mice.

55 Granzyme A mRNA expression was observed in DPPI expressing CD3- CD4- CD8- and CD8+ CD4- thymocytes

56 dition of PR3 restored IL-beta production in DPPI-deficient monocytes.

57 , IL-1beta, and IL-6 in the lung of infected DPPI-/- mice.

58 transfer of DPPI-sufficient neutrophils into DPPI-/- mice restored the levels of CXCL2 and enhanced c

59 transplantation with bone marrow that lacked DPPI or lacked both neutrophil elastase and proteinase 3

60 MC-DPPI maintains its activity for dipeptide substrates at

61 To better define MC-DPPI and to explore the possibility of extracellular rol

62 Dog MC-DPPI has an Mr of approximately 175,000 and consists of

63 an intracellular role for mast cell-DPPI (MC-DPPI) by activating prochymase and protryptase to their

64 phorbol-13-acetate increase expression of MC-DPPI mRNA.

65 ility of extracellular roles, we purified MC-DPPI from mastocytoma cells.

66 ted with ionophore or substance P secrete MC-DPPI in parallel with the granule-associated mediators t

67 of extracellular fluids, suggesting that MC-DPPI may act outside the cell.

68 p to 10 mM NaF had no effect on KLK4, MMP20, DPPI, or cathepsin K activity.

69 We have isolated a cDNA coding for murine DPPI from mouse thymus and spleen cDNA libraries.

70 hromosome hybridization, we localized murine DPPI to chromosome 7D3-E1.1.

71 Chromosome) clones that contained the murine DPPI locus.

72 The absence of DPPI and chymase activity does not affect the growth, gr

73 ng mast cell DPPI reveal that the absence of DPPI in mast cells, rather than in other cell types, is

74 fore, this study defines the consequences of DPPI deficiency for the activation of several immune cel

75 In contrast, inhibition of DPPI during only the last 24 h of 5-day MLC was associat

76 Repeated or delayed inhibition of DPPI in MLC containing granzyme B-deficient responder ce

77 udies, the effects of specific inhibition of DPPI on generation of CTL effector functions were examin

78 tion, when cells isolated from the joints of DPPI(-/-) mice were stimulated in vitro, they had no int

79 accumulation of neutrophils in the joints of DPPI(-/-) mice.

80 gher levels of DPPI mRNA, although levels of DPPI enzymatic activity in CD3- CD4- CD8- thymocytes wer

81 tes expressed significantly higher levels of DPPI mRNA and enzymatic activity than CD4+ CD8+ or CD4+

82 e found to express >40-fold higher levels of DPPI mRNA, although levels of DPPI enzymatic activity in

83 this study, we established that the loss of DPPI activity is associated with severe reduction in the

84 microhardness testing revealed that loss of DPPI expression significantly reduced enamel hardness.

85 The majority of DPPI(-/-) mice were resistant to CIA induction, although

86 e erosions) did develop in a small number of DPPI(-/-) mice.

87 CTL generated in the continuous presence of DPPI inhibition also exhibited impaired lysis of anuclea

88 multiple cellular compartments, the role of DPPI for human serine protease activation is largely und

89 s performed to evaluate the specific role of DPPI(-/-) T lymphocytes.

90 se (mMCP-6) in DPPI -/- BMMCs is 25% that of DPPI +/- BMMCs.

91 Adoptive transfer of DPPI-sufficient neutrophils into DPPI-/- mice restored t

92 These results indicate that DPPI or other DPPI-like protease activities not only are required for

93 e mice from death, may be related to reduced DPPI-mediated activation of mast cell tryptase and other

94 Thus, dog mastocytoma cells secrete DPPI that is active at the pH of extracellular fluids, s

95 The increase in IL-6 in septic DPPI(-/-) mice, which appears to protect these mice from

96 Real-time PCR showed DPPI expression throughout amelogenesis, with highest ex

97 nes was largely unaffected in CII-stimulated DPPI(-/-) splenocytes.

98 ast cell DPPI harms the septic host and that DPPI is a novel potential therapeutic target for treatme

99 We determined that DPPI protein is widely distributed in mouse tissues, alt

100 idyl peptidase I (DPPI) and established that DPPI is required for the full activation of CG, NE, and

101 We find that DPPI -/- mast cells contain normal amounts of immunoreac

102 P) model of septic peritonitis, finding that DPPI(-/-) mice are far more likely to survive sepsis.

103 trast to previous reports, we show here that DPPI mRNA and protein levels and enzymatic activity are

104 These results indicate that DPPI and neutrophils play a critical role in Sendai viru

105 These data indicate that DPPI is expressed at all stages of T cell ontogeny and d

106 These findings indicate that DPPI is not essential for mMCP-6 activation but does inf

107 These results indicate that DPPI or other DPPI-like protease activities not only are

108 These results indicate that DPPI regulates a critical step in the development of CIA

109 ses but no chymase activity, indicating that DPPI is essential for chymase activation and suggesting

110 These findings suggest that DPPI and/or granule-associated serine proteases are nece

111 l for chymase activation and suggesting that DPPI -/- mice are functional chymase knockouts.

112 We demonstrate in vitro that DPPI activates pro-KLK4 to cleave a fluorogenic peptide

113 The DPPI gene consists of seven exons and 6 introns, and spa

114 iated with loss-of-function mutations in the DPPI gene locus.

115 Using DPPI cDNA, we obtained two BAC (Bacterial Artificial Chr

116 In vitro, DPPI also activates mast cell chymases and tryptases.

117 wild-type bone marrow; similarly, in vitro, DPPI-deficient monocytes produced significantly less IL-

118 To determine whether DPPI is essential for their activation in vivo, we used

119 f CD8+ T cell responses to alloantigen, with DPPI mRNA expression peaking on either day 3 or day 4 an

120 Cytotoxic assays with DPPI-/- effector cells reveal severe defects in the indu

121 ly expressed in DPPI(-/-) mice compared with DPPI(+/+) mice.

122 The kidneys of mice reconstituted with DPPI-deficient bone marrow generated significantly less