Kallikrein-kinin system activation in Crohn's disease: differences in intestinal and systemic markers
Abstract
Observations in experimental models and in human ulcerative colitis suggest that activation of the kallikrein-kinin system plays a role in the pathogenesis of inflammatory bowel disease. The aim of this study was to assess activation of the plasma and tissue kallikrein-kinin system in Crohn's disease.We studied plasma inflammatory and contact system parameters in 36 patients with Crohn's disease and in 36 control subjects with noninflammatory GI diseases. We also obtained tissue samples from the involved intestine of 12 patients with Crohn's disease, and from normal peritumoral tissue (12 patients) and diverticulitis tissue (seven patients) as controls. Full-thickness sections were tested for intestinal tissue kallikrein reactivity with a specific antibody.In Crohn's disease patients and controls, plasma levels of prekallikrein, factor XI, high molecular weight kininogen and its cleaved form were normal. Crohn's disease patients had significantly higher levels of antigen and functional Cl-inhibitor (+22%, +12%) than did controls (p = 0.005, p = 0.004). After surgical resection, antigen and functional Cl-inhibitor significantly decreased in Crohn's disease patients (-22%, -15%; p = 0.035, p = 0.006). Intestinal tissue kallikrein immunoreactivity was absent (75%) or weak (25%) in the goblet cells from Crohn's disease tissue sections but was normal in controls, with a highly significant difference in the staining score (p = 0.0001). Intestinal tissue kallikrein immunoreactivity in the interstitium was higher in Crohn's disease than in normal and diverticulitis samples (p = 0.0001 and p = 0.001, respectively).Our observations suggest that intestinal tissue kallikrein is involved in the inflammatory process in Crohn's disease. The lack of contact system activation in peripheral blood might be related to the high plasma levels of Cl-inhibitor, the most important inhibitor of the contact system in the circulation.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In two well-established rodent models of IBS that lead to visceral hyperalgesia, the enhanced visceromotor response to colorectal distension was reversed following administration of F. prausnitzii.
“Using two well-established rodent models of IBS that lead to visceral hyperalgesia in vivo, it was found that the enhanced visceromotor response to colorectal distension was reversed following administration of F. prausnitzii.”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [164]
Faecalibacterium prausnitzii is a potential source of anti-nociceptive mediators, including a PAR-4 activating serine protease.
“Subsequent studies have identified Faecalibacterium prausnitzii as a potential source of anti-nociceptive mediators, including a PAR-4 activating serine protease.”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [164]
Cites
Acute-Phase Proteins and Other Systemic Responses to Inflammation
Gabay, C., & Kushner, I. (1999) · New England Journal of Medicine · doi:10.1056/nejm199902113400607 · Cited by 6,734 · see citing works
Development of a Crohn's Disease Activity Index
Best, W. R., Becktel, J. M., Singleton, J. W., & Kern, F. (1976) · Gastroenterology · doi:10.1016/s0016-5085(76)80163-1 · Cited by 3,152 · see citing works
Inflammatory bowel disease: Etiology and pathogenesis
Fiocchi, C. (1998) · Gastroenterology · doi:10.1016/s0016-5085(98)70381-6 · Cited by 2,059 · see citing works
Proctor, R. R., & Rapaport, S. I. (1961) · American Journal of Clinical Pathology · doi:10.1093/ajcp/36.3.212 · Cited by 989 · see citing works
Hemostasis and Thrombosis: Basic Principles and Clinical Practice
Francis, J. L. (1994) · Blood Coagulation & Fibrinolysis · doi:10.1097/00001721-199410000-00031 · Cited by 729 · see citing works
PATHOGENESIS OF CROHN'S DISEASE: MULTIFOCAL GASTROINTESTINAL INFARCTION
Wakefield, A. J., Dhillon, A. P., Rowles, P. M., Sawyerr, A. M., Pittilo, R. M., Lewis, A. A. M., & Pounder, R. E. (1989) · The Lancet · doi:10.1016/s0140-6736(89)91078-7 · Cited by 573 · see citing works
Kinin Formation: Mechanisms and Role in Inflammatory Disorders
Proud, D., & Kaplan, A. P. (1988) · Annual Review of Immunology · doi:10.1146/annurev.iy.06.040188.000405 · Cited by 416 · see citing works
CURRENT CONCEPTS OF THE ETIOLOGY AND PATHOGENESIS OF ULCERATIVE COLITIS AND CROHN’S DISEASE
Sartor, R. B. (1995) · Gastroenterology Clinics of North America · doi:10.1016/s0889-8553(21)00207-7 · Cited by 384 · see citing works
Polypeptides Which Affect Smooth Muscles and Blood Vessels
(1961) · Archives of Dermatology · doi:10.1001/archderm.1961.01580070180032 · Cited by 260 · see citing works
Activation of the classical pathway of complement by Hageman factor fragment.
Ghebrehiwet, B., Silverberg, M., & Kaplan, A. P. (1981) · The Journal of Experimental Medicine · doi:10.1084/jem.153.3.665 · Cited by 254 · see citing works
Bradykinin stimulates tumor necrosis factor and interleukin‐1 release from macrophages
Tiffany, C. W., & Burch, R. M. (1989) · FEBS Letters · doi:10.1016/0014-5793(89)81331-6 · Cited by 242 · see citing works
Human plasma kallikrein releases neutrophil elastase during blood coagulation.
Wachtfogel, Y. T., Kucich, U., James, H. L., Scott, C. F., Schapira, M., Zimmerman, M. D., Cohen, A. B., & Colman, R. W. (1983) · Journal of Clinical Investigation · doi:10.1172/jci111126 · Cited by 211 · see citing works
Self-citationKININS STIMULATE NET CHLORIDE SECRETION BY THE RAT COLON
Cuthbert, A. W., & Margolius, H. S. (1982) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1982.tb09178.x · Cited by 176 · see citing works
5-HETE: uptake, distribution, and metabolism in MDCK cells
Gordon, J. A., Figard, P. H., Quinby, G. E., et al. (1989) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1989.256.1.c1 · Cited by 137 · see citing works
Contact Activation: A Revision
Schmaier, A. H. (1997) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1657509 · Cited by 103 · see citing works
Berrettini, M., Lämmle, B., White, T., Heeb, M., Schwarz, H., Zuraw, B. L., Curd, J., & Griffin, J. H. (1986) · Blood · doi:10.1182/blood.v68.2.455.455 · Cited by 100 · see citing works
Cugno, M., Cicardi, M., & Agostoni, A. (1994) · Journal of Allergy and Clinical Immunology · doi:10.1016/0091-6749(94)90380-8 · Cited by 90 · see citing works
Self-citationMobilization of tissue kallikrein in inflammatory disease of the colon
Zeitlin, I. J., & Smith, A. N. (1973) · Gut · doi:10.1136/gut.14.2.133 · Cited by 71 · see citing works
The kallikrein-kininogen-kinin system in chronic inflammation
Burch, R. M., Connor, J. R., & Tiffany, C. W. (1989) · Inflammation Research · doi:10.1007/bf01972790 · Cited by 59 · see citing works
Factor XIIIA subunit and Crohn's disease.
Hudson, M. J., Wakefield, A. J., Hutton, R. A., et al. (1993) · Gut · doi:10.1136/gut.34.1.75 · Cited by 50 · see citing works
Immunolocalization of the protease kallikrein in the colon.
Schachter, M., Peret, M. W., Billing, A., et al. (1983) · Journal of Histochemistry & Cytochemistry · doi:10.1177/31.11.6194202 · Cited by 47 · see citing works
Selective plasma kallikrein inhibitor attenuates acute intestinal inflammation in lewis rat
Stadnicki, A., Cadena, R. A. D., Sartor, R. B., Bender, D. E., Kettner, C. A., Rath, H. C., Adam, A. A., & Colman, R. W. (1996) · Digestive Diseases and Sciences · doi:10.1007/bf02091530 · Cited by 37 · see citing works
Self-citationSchremmer, J. M., Blank, M. L., & Wykle, R. L. (1979) · Prostaglandins · doi:10.1016/0090-6980(79)90018-2 · Cited by 35 · see citing works
Complement inhibitors and immunoconglutinins in ulcerative colitis and Crohn's disease.
Potter, B. J., Brown, D. J., Watson, A. G., et al. (1980) · Gut · doi:10.1136/gut.21.12.1030 · Cited by 34 · see citing works
Molecular cloning, purification and in situ localization of human colon kallikrein
Chen, L. M., Richards, G. P., Chao, L., et al. (1995) · Biochemical Journal · doi:10.1042/bj3070481 · Cited by 33 · see citing works
Studies on kallikreins. V. Purification and characterization of rat intestinal kallikrein.
MORIWAKI, C., Fujimori, H., TOYONO, Y., et al. (1980) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.28.3612 · Cited by 13 · see citing works
Oshitani, N., Kitano, A., Nakamura, S., et al. (1988) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365528809090156 · Cited by 8 · see citing works
Friedman, G., & Wild, G. (1996) · Canadian Journal of Gastroenterology and Hepatology · doi:10.1155/1996/421094 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The emerging roles of bacterial proteases in intestinal diseases
Caminero, A., Guzman, M., Libertucci, J., & Lomax, A. E. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2181922 · Cited by 92 · see citing works
- Authors
- Devani, M., Cugno, M., Vecchi, M., Ferrero, S., Berardino, F., Avesani, E. C., Franchis, R., & Colman, R. W.
- Affiliations
- University of Milan (IT)
- Temple University (US)
- Venue
- The American Journal of Gastroenterology
- Published
- 2002-08
- Volume
- 97
- Issue
- 8
- Pages
- 2026-2032
- ISSN
- 0002-9270 (ISSN-L)
- 1572-0241
- OpenAlex
- W1992041647
- Cited by
- 31
- References
- 28
- Citations by year
- 2023: 3 · 2021: 1 · 2019: 1 · 2018: 3 · 2015: 1 · 2013: 1
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Medicine › Genetics › Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Keywords
- kallikrein-kinin system, Crohn's disease, contact system, C1 inhibitor, goblet cells, inflammatory bowel disease, diverticulitis, surgical resection, prekallikrein, factor XI, high molecular weight kininogen
- MeSH terms
- Adult, Aged, Complement C1 Inactivator Proteins, Crohn Disease, Factor XI, Female, Humans, Immunohistochemistry, Kininogens, Male, Middle Aged, Case-Control Studies, Statistics, Nonparametric, Tissue Kallikreins, Plasma Kallikrein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
