ACE, see angiotensin-converting enzyme

(1)

339 Index

ACE, see angiotensin-converting enzyme

ACE-2, see angiotensin-converting enzyme-2

Acinar cells cell biology, 90f pathophysiology, 91ff proteases in pancreatitis, 91ff Acute rejection, 220ff

ADAM, see A Disintegrin And Metalloproteinase

A Disintegrin And Metalloproteinase characteristics, role in IBD, 235 Allodynia, 124 Angiotensin

liver fibrosis, 194 processing, 135 receptors, 135ff, 195f receptor blocker, 143

Angiotensin-converting enzyme gut inflammation, 301ff liver fibrosis, 183ff, 192ff polymorphism, 304, 308f stellate cells, 184

structure, 133f, 184f

Angiotensin-converting enzyme-2, 134f, 185

Apical protein transport, 315ff Barrett’s metaplasia, 63 Batimastat, 47

Bradykinin, 196f, 305f Cathepsin

cathepsin B, 69f, 75, 92, 97 cathepsin D, 69, 75

cathepsin E, 70 cathepsin G, 6 cathepsin H, 69 cathepsin K, 70 cathepsin L, 69f, 75 cathepsin W, 70f

CD10, see neutral endopeptidase CD13, see membrane alanyl-

aminopeptidase

CD26, see dipeptidyl peptidase IV CDX, 63f

Chemokines

angiogenesis, 263ff biology, 257ff classification, 259

colorectal cancer, 258ff, 271

interaction with MMPs, 285ff

inhibitors, 193f, 304

(2)

metastasis, 267ff therapeutic use, 269ff tumor growth, 265f Collagenases

gastric cancer, 44ff liver disease, 209ff CP-471,358, 49 Diabetes

classification, 143

islet cell transplantation, 145 local renin-angiotensin system,

143ff

role of DPIV, 329ff symptoms, 143 Dipeptidyl peptidase IV

deficiency, 325ff diabetes, 329ff

enzymatic activity, 327ff expression, 323

Fischer 344 rat, 325f gastric cancer, 63 IBD, 331ff inhibitors, 330f sorting signals, 324 structure, 323f, 326

subcellular localization, 327 transport of, 316, 323ff

DPIV, see dipeptidyl peptidase IV Epithelial cell

protein sorting, 317 Fibrosis

chronic pancreatitis, 102ff cytokines, 187ff

hepatic stellate cells, 186ff liver fibrosis, 183ff pathogenesis, 185ff Gastric cancer

cell lines, 62 classification, 34 diagnosis, 33

Helicobacter pylori, 46, 61ff

incidence, 33

molecular markers, 34 therapy, 33

Gastroesophagal reflux disease, 61 Gelatinases

gastric cancer, 39ff, liver disease, 209ff

GERD, see gastroesophagal reflux disease

HCC, see hepatocellular carcinoma HCV, see hepatitis C virus

Helicobacter pylori diseases, 65ff, 69 gastritis, 68f

induction of MMPs, 72f

in vitro models of infection, 77f proteases of, 66f

ulcer disease, 73f Hepatic stellate cells

activation in liver fibrosis, 186f signaling pathwys, 189ff Hepatitis

incidence, 153 therapy, 153 Hepatitis C virus

cell entry, 155

genome organization, 156 hepatitis, 153

inhibitors, 153ff life cycle, 157 proteases, 153ff, 157f replication, 154f replicon assay, 172 Hepatocellular carcinoma

MMPs, 209ff

IBD, see inflammatory bowel disease

Inflammatory bowel disease

angiotensin, 303ff, 307ff

bradykinin, 303ff

pathophysiology, 301

substance P, 307ff

(3)

Knock-out mouse ACE-2, 185 cathepsin B, 92, 97 MAS receptor, 185 MMP-9, 227 p47

^phox

, 195 PAR-1, 3 SLPI, 71 TLR4, 94

Liver transplantation, 217ff Marimastat, 47ff

Matrix metalloproteinase activation, 38f, 211ff, 237f,

272f

antisense-oligonucleotides, 51 biological activity, 37

characteristics, 210, 213 chemokine interaction, 285ff chronic liver disease, 209ff classification, 35, 210 colon cancer, 278ff detection methods, 213f expression, 236f

in cancer, 35ff, 108ff, 255ff, 273ff

in gastric cancer, 39ff in IBD, 235ff, 238ff

inhibitors, natural 38ff, 212, 282ff

inhibitors, synthetic, 47ff liver fibrosis, 214ff liver transplantation, 209ff MMP-1, 97ff, 103f, 275

MMP-2, 39ff, 108f, 209ff, 218ff, 238f, 275f

MMP-3, 238, 276 MMP-7, 42ff, 240, 276f

MMP-9, 39ff, 109, 209ff, 218ff, 277f

MMP-10, 240 MMP-12, 281

MMP-14, 238, 281f MMP-15, 109 MMP-19, 240, 282 MMP-26, 240 pancreatitis, 97ff pancreatic cancer, 108ff substrates, 35f, 37, 108, tumor progression, 36

Membrane alanyl-aminopeptidase, 74

MMP, see matrix metalloproteinase Neutral endopeptidase, 74

Non-steroidal antiinflammatory drugs, 61

NSAID, see non-steroidal anti- inflammatory drugs Pain

allodynia, 124 inflammation, 124 sensitization, 124 role of PARs, 125f role of trypsin, 125 Pancreas

cell types, 131 functions, 131f tissue structure, 131 Pancreatic cancer, 104ff Pancreatitis

acute, 89ff, 142, aetiology, 89, 123 cell death pathways, 98 chronic, 100ff, 123ff cereluein/induced, 99 incidence, 89, 123

inflammatory cytokines, 94 mortality, 89

pain, 123ff proteases, 89ff

sentinel acute pancreatitis event (SAPE), 101

trypsinogen, 95 MMP-13, 281

inhibition of, 50ff

(4)

PAR, see Protease-activated receptor

Plasminogen activator, 110ff Polymorphism

MMP-2, 40, 225 MMP-3, 44 MMP-9, 225 Proteases

angiogenesis, 111ff assays, 165ff colon cancer, 20f fibrosis, 20

Helicobacter pylori-mediated disease, 61ff

inhibitors, 167ff N3/4A, 161ff

pancreatic cancer, 108ff pancreatic inflammation and pain, 19ff

pancreatitis, 15ff, 89ff stomach disease, 21f viral, 157ff

Protease-activated receptor activation, 2, 4ff

agonists, 4, 6 cloning of, 2

expression in the gastrointestinal tract, 8ff

gastrointestinal diseases, 1ff, 22 gastrointestinal functions, 9ff,15 inflammatory proteases,

internalization, 8 ion transport, 9f knock-out mouse, 3, 14

membrane proteases, activation by, 7

microbial proteases, activation by, 7f

motility, gastrointestinal, 11f nociception, 127ff

pancreatic pain, 125ff

paracellular permeability, 10f

proteolytic cleavage site, 2 proteolytic inactivation, 4 secretion, 12ff

thrombin-binding, 2 trypsin, activation by, 5f

RAS, see Renin-angiotensin system Reactive oxygen species

liver fibrosis, 187 pancreatitis, 143

Rejection activity index, 221 Renin-angiotensin system

circulating RAS, 132ff components, 132f functions, 132f local RAS, 137ff

pancreatic disease, 131ff, 137ff, 141ff

regulation 132f, 138f

ROS, see reactive oxygen species Secretory leukocyte proteinase inhibitor, 67, 71

SLPI, see secretory leukocyte proteinase inhibitor

Stomach anatomy, 63 cancer, 33ff, 61ff Helicobacter pylori, 61ff proteases, physiological, 64f Sucrose-isomaltase