ライフサイエンスコーパス: cathepsin S

1 notable upregulation of Ctss (which encodes cathepsin S).

2 the substrate-binding subsites S3 to S1' of cathepsin S.

3 l intermolecular contacts that are unique to cathepsin S.

4 involves endocytic compartments enriched in cathepsin S.

5 gamma inducing factor, apolipoprotein E, and cathepsin S.

6 d fibroblasts expressed detectable levels of cathepsin S.

7 atment with a variety of proteases including cathepsin S.

8 cathepsin L, but distinctly less stable than cathepsin S.

9 eavage, most likely by the cysteine protease cathepsin S.

10 an evolutionarily related cysteine protease, cathepsin S.

11 activity of the lysosomal cysteine protease, cathepsin S.

12 designed to explore the S3 binding pocket of cathepsin S.

13 gned to target the homologous human protease cathepsin S.

14 rovided inhibitors with moderate potency for cathepsin S.

15 dehyde inhibitors with nanomolar affinity to cathepsin S.

16 staining for the powerful elastolytic enzyme cathepsin S.

17 A1, A2, and A3 (Stfa1-Stfa3), inhibitors of cathepsin S, a cysteine protease required for autoantige

18 Cathepsin S, a lysosomal cysteine protease of the papain

19 We show that the cysteine protease cathepsin S activates MrgprC11 and evokes receptor-depen

20 nscriptional mediator of IFN-gamma-dependent cathepsin S activation.

21 highly potent cathepsin K inhibitor but with cathepsin S activity and very poor stability to microsom

22 of Ii, revealing MHC class II haplotype and cathepsin S activity as regulators of NK T cells.

23 or the existence of specific localization of cathepsin S activity in dendritic cells.

24 lls from IRF-1(-/-) mice fail to up-regulate cathepsin S activity in response to IFN-gamma.

25 e demonstrate that G-CSF injection increases Cathepsin S activity in spinal cord tissues.

26 Cathepsin S activity is essential for complete processin

27 Unique among cysteine proteases, cathepsin S activity is up-regulated by IFN-gamma.

28 Cs, inefficient Ii chain cleavage due to low cathepsin S activity leads to the transport of class II-

29 to lysosomes, while in mature DCs, elevated cathepsin S activity results in efficient delivery of cl

30 Interestingly, cathepsin S activity was strongly up-regulated in sample

31 etermine whether pharmacologic inhibition of cathepsin S activity would ameliorate symptoms of coliti

32 d identified vesicles containing exclusively cathepsin S activity.

33 ation of HLA-DR was not explained by altered cathepsin S activity.

34 Here, we show that the cysteine protease cathepsin S acts in a concerted fashion with other cyste

35 Furthermore, cathepsin S affected the production of type IV collagen-

36 In the structure of the cathepsin S-aldehyde complex, the tetrahedral thiohemiac

37 athepsin S inhibition and a null mutation of cathepsin S also decreased IFN-gamma-induced DNA injury,

38 thermostability while inhibiting cleavage by cathepsin S, an endosomal protease essential for antigen

39 anscription-PCR showed a >4-fold increase in cathepsin S, an enzyme important in antigen presentation

40 l forms (1.5 and 1.9 A) of a complex between cathepsin S and a triazole inhibitor incorporating a chl

41 To investigate the contribution of cathepsin S and cathepsin X to colitis, we induced colit

42 okines IL-1beta or IFN-gamma secreted active cathepsin S and degraded substantial insoluble elastin (

43 )-22 proved to be potent inhibitors of human cathepsin S and exhibited notable selectivity over human

44 ose the X-ray structure of a complex between cathepsin S and inhibitor 2 which reveals an unprecedent

45 using dramatic build-up of the p8 product of Cathepsin S and interfering with earlier steps in CD74 e

46 ins crucial for antigen presentation, namely cathepsin S and invariant chain, was determined.

47 ze allergen and expressed marginal levels of cathepsin S and invariant chain.

48 re analyzed for the presence and activity of cathepsin S and its endogenous inhibitors.

49 ases (MMP-2, MMP-9), cysteine endoproteases (cathepsin S and K), and interleukin-1beta, a cytokine th

50 LY3000328 provoked a clear upregulation of cathepsin S and L activity in the mucosa, most likely th

51 leavage sites of the endolysosomal proteases cathepsin S and legumain.

52 I and IL6, lesion matrix-degrading proteases cathepsin S and matrix metalloproteinase-9, and systemic

53 Cathepsin S and TGF-beta1 were elevated more than 15-fol

54 in a reaction in which the cysteine protease cathepsin S and the accessory molecule H-2DM play an ess

55 e MHC class II endosomal processing pathway, cathepsin S and the invariant chain, in the normal funct

56 modest increase in mucosal activity of both cathepsin S and X compared to naive mice.

57 -Le(X) neither required TAP-transporters nor Cathepsin-S and was still observed after prolonged intra

58 sin-deficient B cells to examine the role of cathepsins S and B in the degradation of other molecules

59 tantly, the levels of IL-18 and its targets, cathepsins S and B, were increased in pulmonary macropha

60 Cathepsins S and K are potent mammalian proteases secret

61 mined the expression of the potent elastases cathepsins S and K in human atheroma.

62 Elastolytic cysteine proteases, including cathepsins S and K, are overexpressed at sites of arteri

63 ver, macrophages from mice deficient in both cathepsins S and L can process Ii and load peptides onto

64 s of specific cysteine proteases, especially cathepsins S and L, in degrading the invariant chain and

65 eine protease with high sequence homology to cathepsins S and L, members of the papain superfamily of

66 as found to be intermediate between those of cathepsins S and L.

67 ization of cathepsin K is similar to that of cathepsins S and L.

68 n K, a novel cysteine protease homologous to cathepsins S and L; ESTs for other cathepsins were rare.

69 hree subunits of complement C1q, lysozyme M, cathepsins S and Z, cytochrome b558 small subunit, macro

70 ctor, tumor necrosis factor alpha, legumain, cathepsin S, and A disintegrin and metalloprotease 17 ex

71 tivity/protein of the elastolytic proteases, cathepsin S, and metalloproteinase-9.

72 herosclerotic mediators, like Calgranulin A, Cathepsin S, and Osteopontin.

73 three CJD models, the upregulation of CCR5, cathepsin S, and TGF-beta1 was variable with respect to

74 mokine receptor CCR5, the lysosomal protease cathepsin S, and the pleiotropic cytokine transforming g

75 whereas glial fibrillary acidic protein and cathepsin S are up-regulated throughout the entire neoco

76 inflammatory plasma proteins, we identified cathepsin S as a lead indicator of liver disease.

77 Systemic inhibition of cathepsin S attenuates the progression of atheroscleroti

78 A selective inhibitor of cathepsin S blocked > 80% of this elastolytic activity.

79 cificity of human cathepsin O2 is similar to cathepsin S but distinguished from cathepsins L and B.

80 Purified cathepsin S, but not cathepsin B, H, or D, specifically

81 Collectively, these results suggest that cathepsin S, but not cathepsin X, may contribute to some

82 Inhibition of cathepsin S by HCV proteins increased cell surface expre

83 These genes are cathepsin S, C1q B-chain of complement (C1qB), beta2-mic

84 rved from hydrolysis when a 10-fold ratio of cathepsin S cannibalized the highly collagenolytic cathe

85 This study tested the hypothesis that cathepsin S (Cat S) contributes to angiogenesis.

86 f myasthenia gravis, we examined the role of cathepsin S (Cat S) in experimental autoimmune myastheni

87 overexpress the lysosomal cysteine protease cathepsin S (Cat S), one of the most potent mammalian el

88 e former use the lysosomal cysteine protease cathepsin S (Cat S), whereas thymic cortical epithelial

89 Cathepsin S (Cat-S) is a lysosomal cysteine protease of

90 zed a pathogenic role in this dysfunction of cathepsin S (Cat-S), a cysteine protease that degrades e

91 Similar to cathepsin S, cathepsin O2 is characterized by a bellshap

92 In contrast to cathepsin L, but similar to cathepsin S, cathepsin V exhibited only a very weak coll

93 Pharmacological inhibition of cathepsin S (CatS) allows for a specific modulation of t

94 Cathepsin S (CATS) and cathepsin H (CATH) activities wer

95 Cathepsin S (catS) and cathepsin L (catL) mediate late s

96 egradation by different proteases, including cathepsin S (CatS) and the intramembrane protease signal

97 covalent inhibitors of the cysteine protease cathepsin S (CatS) are described.

98 decreasing a proposed tear biomarker of SjS, cathepsin S (CATS) compared to free drug.

99 ce lacking the lysosomal cysteine proteinase cathepsin S (catS) demonstrated a profound inhibition of

100 We have dissected the role of cathepsin S (CatS) in the trafficking and maturation of

101 uated by prolonged intrathecal delivery of a cathepsin S (CatS) inhibitor and a fractalkine (FKN) neu

102 rocess that was blocked by chloroquine and a cathepsin S (CatS) inhibitor; brefeldin A (BFA) also blo

103 -phenyl (LHVS), an irreversible inhibitor of cathepsin S (CatS) whose proteolytic activity is also in

104 imaging to test the hypothesis in vivo that cathepsin S (catS), a potent elastolytic proteinase, acc

105 00-fold selective versus cathepsin B (CatB), cathepsin S (CatS), and trypsin-like as well as PGPH-lik

106 The potent protease cathepsin S cleaves elastin and generates bioactive elas

107 ve site loop and detection of a stable SCCA1-cathepsin S complex by sodium dodecyl sulfate-polyacryla

108 The t1/2 of SCCA1-cathepsin S complexes was >1155 min, whereas that of cys

109 Measurements and Main Results: Pulmonary cathepsin S concentrations and activity were elevated in

110 Conclusions: Cathepsin S contributes to acute lung injury and may rep

111 al lysosomal proteases, cathepsin L (CL) and cathepsin S (CS), have been shown to process invariant c

112 to Galpha(q), Galpha(s), and beta-arrestins, cathepsin-S (CS) and neutrophil elastase (NE) cleave PAR

113 Cathepsin S (CTSS) activity is increased in bronchoalveo

114 tients with PDAC, create a microdomain where cathepsin S (CTSS) cleaves human (h)ARG1 into different

115 suggest relevance between cysteine protease cathepsin S (CTSS) expression and SLE.

116 ta suggest a role for the lysosomal protease cathepsin S (CTSS) in type 1 diabetes.

117 Cathepsin S (Ctss) is a cysteine protease that is active

118 Cathepsin S (CTSS) is a cysteine protease that is consti

119 Cathepsin S (CTSS) is a lysosomal cysteine protease with

120 Cathepsin S (CTSS) is a widely expressed cysteinyl prote

121 Cathepsin S (CTSS) is highly increased in Sjogren's synd

122 MHC II, IFN-gamma, IL-1beta, TNF-alpha, and cathepsin S (Ctss) mRNA transcripts, and greater nitroty

123 r levels of MHC II, IFN-y, IL-1B, TNF-a, and cathepsin S (Ctss) mRNA transcripts, and greater nitroty

124 1) repressed expression of the gene encoding cathepsin S (Ctss), a cysteine protease that cleaves inv

125 Activity of cathepsin S (CTSS), a cysteine protease, is significantl

126 nt up-regulation of genes encoding proteases cathepsin S (CTSS), mast cell chymase (CMA1), tryptase (

127 arcinoma (HCC) cells preferentially secreted cathepsin S (CTSS), which regulates liver TICs through t

128 nse to type 2 immunity in the gut, driven by Cathepsin S (CTSS)-mediated cleavage.

129 teraction that responds to G-CSF by engaging Cathepsin S-CX3CR1-inducible NOS signaling.

130 accumulates within endocytic compartments of cathepsin S(-/-) DCs.

131 y implicated, we demonstrated that selective cathepsin S deficiency impaired angiogenesis and tumor c

132 While cathepsin S-deficient mice exhibited less rectal bleedin

133 Although cathepsin S-deficient mice have normal numbers of B and

134 Cathepsin S-deficient phagosomes generate a class I-pres

135 ity is further supported by the finding that cathepsin S degrades a number of extracellular matrix mo

136 These studies demonstrate that cathepsin S-dependent epithelial cell apoptosis is a cri

137 mma-Ser18, identified as the main product of cathepsin S-dependent IL-36gamma cleavage, induced psori

138 mples (P < 0.001), whereas the expression of cathepsin S did not significantly differ in these diseas

139 Cathepsin S-digested allergenic lipocalins, but not dige

140 synthesized on solid support, incorporate a cathepsin S dipeptide substrate (Leu-Arg), and a poly(et

141 Upon proteolytic activation with cathepsin S (EC 3.4.22.27), CyPEG-2 showed greater than

142 is structural plasticity of the S2 pocket in cathepsin S explains the selective inhibition of catheps

143 ion of macrophage-like P388D cells and other cathepsin S-expressing cells.

144 CD4(+)HLA-DR(+) T cells down-regulated cathepsin S expression and activity 18 h after activatio

145 Furthermore, cathepsin S expression and activity, and concordantly ce

146 y, we examined the effect of HCV proteins on cathepsin S expression and found it to be markedly decre

147 Cathepsin S expression in macrophage-like synoviocytes s

148 In contrast, cathepsin S expression was restricted to CD68+ macrophag

149 ate the pathway by which IFN-gamma increases cathepsin S expression.

150 senting cells of mice that lack the protease cathepsin S fail to process Ii beyond a 10 kDa fragment,

151 The SFRP2(+) fibroblasts also express cathepsin S, further amplifying inflammatory responses b

152 Rationale: Although the cysteine protease cathepsin S has been implicated in the pathogenesis of s

153 While cathepsin S has potential to be a therapeutic target in

154 Mice whose APC lack cathepsin S have reduced crosspriming to particulate and

155 ding, possibly by targeting ADAM10/17 and/or cathepsin S, have potential as peripheral approaches for

156 Increased cathepsin S immunofluorescence was detected in lysosomes

157 Specific inhibition of cathepsin S in A20 cells markedly impaired presentation

158 Objectives: To characterize the status of cathepsin S in acute lung inflammation and examine the r

159 ased levels of precursor and mature forms of cathepsin S in agLDL-VSMC.

160 m laminin-5, revealing a functional role for cathepsin S in angiogenesis and neoplastic progression.

161 Specific inhibition of cathepsin S in B lymphoblastoid cells prevented complete

162 xes, whereas cathepsin F was as efficient as cathepsin S in CLIP generation.

163 hree-dimensional crystal structures of human cathepsin S in complex with potent covalent inhibitors,

164 Thus, the ratio of cystatin C to cathepsin S in developing DCs helps to determine the fat

165 te lung inflammation and examine the role of cathepsin S in disease pathogenesis.

166 colitis compared to healthy controls, while cathepsin S in mucosal biopsies was unchanged.

167 We observed a significant increase in fecal cathepsin S in patients with ulcerative colitis compared

168 ce in vivo selectively inhibited activity of cathepsin S in splenocytes, resulting in accumulation of

169 ture thiol reductase, but suggest a role for cathepsin S in the turnover of mature GILT and in regula

170 Thus, inhibition of cathepsin S in vivo alters Ii processing, antigen presen

171 ecause antagonism of this receptor abrogated cathepsin S-induced airway inflammation.

172 Selective cathepsin S inhibition and a null mutation of cathepsin

173 We hypothesized that selective cathepsin S inhibition attenuates atherogenesis in hyper

174 here examine the functional significance of cathepsin S inhibition on antigen presentation and immun

175 expression and localization of an endogenous cathepsin S inhibitor cystatin C.

176 Furthermore, cathepsin S inhibitor or siRNA significantly decreased e

177 6.6 or 60 mg/kg of the potent and selective cathepsin S inhibitor RO5444101 or a control diet.

178 molecular weight (414 Da) and potent (15 nM) cathepsin S inhibitor that showed >1000-fold selectivity

179 lar weight (304 Daltons) and potent (9.6 nM) cathepsin S inhibitor that showed from 100- to >1000-fol

180 Administration of a cathepsin S inhibitor to mice in vivo selectively inhibi

181 ved through transgenic mice, or the use of a cathepsin S inhibitor, significantly reduces neuroinflam

182 e, modular synthesis of compound 1, a potent Cathepsin S inhibitor.

183 we report a series of potent and reversible Cathepsin S inhibitors based on dipeptide nitriles.

184 Direct cathepsin S instillation into the lungs induced key path

185 Cathepsin S is a cysteine protease that has been implica

186 Cathepsin S is a cysteine protease with potent endoprote

187 Cathepsin S is a lysosomal cysteine protease and control

188 These results indicate cathepsin S is a major Ii-processing enzyme in splenocyt

189 f a reversible inhibitor cocrystallized with Cathepsin S is also reported.

190 These data suggest that cathepsin S is an important player in degenerative disor

191 Thus, cathepsin S is essential in B cells for effective li pro

192 The cysteine protease cathepsin S is highly expressed in malignant tissues.

193 The cysteine protease cathepsin S is highly expressed in spleen, lymphocytes,

194 ely express class II MHC, we determined that cathepsin S is necessary for invariant chain proteolysis

195 Cathepsin S is not controlled transcriptionally but by a

196 Cathepsin S is one of the most important cysteine protei

197 Rationale: CTSS (cathepsin S) is a cysteine protease that is observed at

198 The effects of cathepsin S knockout and pharmacological inhibition were

199 pain cysteine protease superfamily including cathepsins S, L, and B and is selectively expressed in o

200 highly expressed selecively in osteoclasts; cathepsins S, L, and B were not detectable.

201 endritic cells lacking the cysteine protease cathepsin S lack the TAP-independent pathway.

202 Effector genes namely Eng-1, Cathepsin S-like cysteine protease, cellulase, and two u

203 els of the inflammatory markers lysozyme and cathepsin S may enable detection of multiple distinct st

204 Cathepsin S may partly mediate its pathogenic effects vi

205 activation of IL-36gamma and highlight that cathepsin S-mediated activation of IL-36gamma may be imp

206 f conventional protease-activated receptors, cathepsin S-mediated activation of MrgprC11 did not invo

207 sm was used to test a possible mechanism for cathepsin S-mediated inflammation.

208 suggested that HCV has an inhibitory role on cathepsin S-mediated major histocompatibility complex (M

209 dicate that differences in susceptibility to cathepsin S-mediated sigma3 processing are responsible f

210 acid-independent lysosomal cysteine protease cathepsin S mediates outer capsid processing in macropha

211 The cysteine endoprotease, cathepsin S, mediates Ii degradation in human and mouse

212 I-A(k), cathepsin S(-/-) mice do not accumulate class II-associa

213 In vitro, thymic dendritic cells (DCs) from cathepsin S(-/-) mice exhibit defective presentation of

214 stent with these data, we demonstrate, using cathepsin S(-/-) mice, that although the anti-PC respons

215 TNF-alpha induced cathepsin S, MMP-1, -3, and -9 mRNA expression in a dose

216 revealed that 10 ng/ml of TNF-alpha induced cathepsin S, MMP-1, -3, and -9 mRNA expression with the

217 Inhibition of cathepsin S molecules, blockade of costimulation through

218 l degeneration and reactive synaptogenesis), cathepsin S mRNA is dramatically increased in activated

219 dult rat brain, spleen, and lung reveal that cathepsin S mRNA is preferentially expressed in cells of

220 overexpression of IRF-1 increases endogenous cathepsin S mRNA levels in 293T epithelial cells.

221 s with increased levels of IRF-1 protein and cathepsin S mRNA.

222 the invariant chain (Ii) processing enzyme, cathepsin S, NK1.1(+) T cell selection and function are

223 Our data indicate that neither cathepsin S nor B is critical for H-2M degradation or pr

224 growth factor levels were also increased in cathepsin S-null mice.

225 igen presenting cells, and mice deficient in cathepsin S or cathepsin L exhibit severely impaired ant

226 s of bovine serum albumin generated by human cathepsin S or neutrophil elastase and into a fragment o

227 Cathepsins S or L are known to be required for the final

228 carcinoma tissue extracts did not change in cathepsin S- or cystatin C-null mice, tumor tissue basic

229 epsin S explains the selective inhibition of cathepsin S over cathepsin K afforded by inhibitors with

230 ased cleavage efficiency and selectivity for cathepsin S over cathepsins B, L, and K.

231 trated that RO5444101 reduced immunoreactive cathepsin S (P < 0.05), elastin degradation (P = 0.01),

232 The cysteine protease Cathepsin S performs a fundamental step in antigen prese

233 Therefore, cathepsin S plays a major role in generating presented p

234 de each other as well as the substrate, with cathepsin S predominantly degrading cathepsin K.

235 psin S-sufficient phagosomes and recombinant cathepsin S produce the mature epitope.

236 human vascular cells leads to an increase in cathepsin S production concomitantly with a decrease in

237 n of IRF-1, but not IRF-2, markedly augments cathepsin S promoter activity in A549 cells.

238 Our data demonstrate that the cathepsin S promoter contains an IFN-stimulated response

239 nd prophylactic or therapeutic inhibition of cathepsin S reduced neutrophil recruitment and protein l

240 a specific fragment from the protease gene, cathepsin S (Rs-cps), was cloned into the binary vector

241 Among the cysteine proteases, cathepsin S seems to be best suited for such a process s

242 ization of the probe with CD68, elastin, and cathepsin S, similar to that observed in the experimenta

243 s with Lang virions were also inhibited by a cathepsin S-specific inhibitor.

244 Importantly, the deficiency of cathepsin S specifically in LECs, achieved through trans

245 In contrast, cathepsin S-sufficient phagosomes and recombinant cathep

246 of NH(4)Cl, cell lines engineered to express cathepsin S supported infection by Lang, but not c43, vi

247 ined expression of the elastinolytic enzyme, cathepsin S, the collagen metabolizing matrix metallopro

248 t, which is the binding affinity hot spot of cathepsin S, the Phe211 side chain can assume two stable

249 enzyme inhibitors, was previously applied to cathepsin S to obtain a novel (2-arylphenoxy)acetaldehyd

250 enzyme inhibitors, was previously applied to cathepsin S to obtain low nanomolar 1,4-disubstituted-1,

251 cidic protein, complement component C1q, and cathepsin S, up-regulation of which has been associated

252 eal time PCR and protein analyses identified cathepsin S, W, and C activity at sites of leukocyte pen

253 Luminal secretion of cathepsin S was dramatically increased upon colitis indu

254 olecule inhibitors and siRNA gene silencing, cathepsin S was identified as the major IL-36gamma-activ

255 Recombinant cathepsin S was instilled directly into the lungs of mic

256 The downregulation of cathepsin S was mediated by HCV core and NS5A proteins i

257 eversible inhibitor of the cysteine protease cathepsin-S was prepared on large scale using a converge

258 of cathepsin F, the functional synergist of cathepsin S, was not observed.

259 CD74 and cathepsin S were among the common genes down-regulated i

260 Matrix metalloprotease 2 (MMP-2) and cathepsin S were present at baseline and were significan

261 -based probe (qABP) that selectively targets cathepsin S which is highly expressed in immune cells.

262 In contrast, cathepsin S, which does not form complexes with chondroi

263 uccessfully applied to the cysteine protease cathepsin S, which is implicated in autoimmune diseases.

264 nnover Functional Capacity Questionnaire and cathepsin S whose expression is limited to CD-68-positiv

265 CIITA-transfected astrocytes did not express cathepsin S without IFN-gamma activation, indicating tha

266 pro-inflammatory roles, we hypothesized that cathepsin S would drive other symptoms associated with I