The Kallikrein–Kinin system

Hillmeister, Philipp; Persson, Pontus B.

doi:10.1111/apha.12007

Cited by 48 publications

(51 citation statements)

References 47 publications

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“…The serine protease tissue kallikrein-1 (KLK-1) and its cleavage products lys-bradykinin and bradykinin, are critical components of the kallikrein-kinin system (KKS) [5], [6]. The KKS exerts physiological effects through binding of kinin peptides to the bradykinin 1 and bradykinin 2 receptors [7], [8].…”

Section: Introductionmentioning

confidence: 99%

Autoimmune Diabetes Is Suppressed by Treatment with Recombinant Human Tissue Kallikrein-1

et al. 2014

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The kallikrein-kinin system (KKS) comprises a cascade of proteolytic enzymes and biogenic peptides that regulate several physiological processes. Over-expression of tissue kallikrein-1 and modulation of the KKS shows beneficial effects on insulin sensitivity and other parameters relevant to type 2 diabetes mellitus. However, much less is known about the role of kallikreins, in particular tissue kallikrein-1, in type 1 diabetes mellitus (T1D). We report that chronic administration of recombinant human tissue kallikrein-1 protein (DM199) to non-obese diabetic mice delayed the onset of T1D, attenuated the degree of insulitis, and improved pancreatic beta cell mass in a dose- and treatment frequency-dependent manner. Suppression of the autoimmune reaction against pancreatic beta cells was evidenced by a reduction in the relative numbers of infiltrating cytotoxic lymphocytes and an increase in the relative numbers of regulatory T cells in the pancreas and pancreatic lymph nodes. These effects may be due in part to a DM199 treatment-dependent increase in active TGF-beta1. Treatment with DM199 also resulted in elevated C-peptide levels, elevated glucagon like peptide-1 levels and a reduction in dipeptidyl peptidase-4 activity. Overall, the data suggest that DM199 may have a beneficial effect on T1D by attenuating the autoimmune reaction and improving beta cell health.

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Section: Introductionmentioning

confidence: 99%

Autoimmune Diabetes Is Suppressed by Treatment with Recombinant Human Tissue Kallikrein-1

et al. 2014

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“…In this study, the rat plasma proteome showed changes in proteins related to the kallikrein-kinin system such as C1 inhibitor, kininogen-1, carboxypeptidase N subunit 2, and complement factors B, C3, and C4. The kallikrein-kinin system has renal (diuretic), cardiovascular (vasodilatation), and immunological (regulation of inflammatory processes) functions [27]. It has been demonstrated that STZ-induced hyperglycemia affects the kallikrein-kinin system, reduces cardiac and renal kallikrein, and therefore reduces kinins and contributes to diabetic nephropathy [28].…”

Section: Discussionmentioning

confidence: 99%

Consumption of Amaranth Induces the Accumulation of the Antioxidant Protein Paraoxonase/Arylesterase 1 and Modulates Dipeptidyl Peptidase IV Activity in Plasma of Streptozotocin-Induced Hyperglycemic Rats

et al. 2017

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Background/Aim: Amaranth is a source of several bioactive compounds, among which peptides with inhibitory activity upon dipeptidyl peptidase IV (DPP-IV) have been reported. However, there is no information about the action of amaranth DPP-IV-inhibitory peptides using in vivo models. The aim of this work was to evaluate the effect of amaranth consumption on plasma and kidney DPP-IV activity as well the changes in plasma proteome profile of streptozotocin (STZ)-induced hyperglycemic rats. Methods: Rats were fed for 12 weeks with a diet containing 20% popped amaranth grain. Kidneys and blood samples were collected for lipid profile, DPP-IV activity and expression, and proteomic analysis. Results: Total cholesterol and DPP-IV activity in plasma was increased in hyperglycemic rats, but this effect was reverted by amaranth consumption. Triacylglycerols were increased in the hyperglycemic group fed amaranth, and the highest levels of high-density lipoproteins were also observed in this group. These data correlated with the accumulation of apolipoprotein A-II in plasma. Accumulation of the antioxidant protein paraoxonase/arylesterase 1 in STZ-induced hyperglycemic rats was observed when amaranth was supplied in the diet. Conclusion: This study provides new insights into the molecular mechanisms by which amaranth exerts its beneficial health action in a hyperglycemic state.

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“…In contrast to B1R, B2R is constitutively expressed. Many studies showed that B1R and B2R are the major down-stream effectors of KKS (Hillmeister and Persson 2012). The study, therefore, examined expressions of B1R and B2R in the kidney at both the mRNA and protein level to gain further insight into KKS-mediated immune renal injury induced by TCE.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to B2R, B1R is weakly expressed in physiological condition, but increased during inflammatory response. A recent report showed that the recruitment of inflammatory cells was reduced when B1R or B2R was blocked or deleted in experimental models of inFammation (Hillmeister and Persson 2012).…”

Section: Introductionmentioning

confidence: 99%

Plasma Kallikrein-Kinin system mediates immune-mediated renal injury in trichloroethylene-sensitized mice

Wang

Zhang

et al. 2016

Journal of Immunotoxicology

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Trichloroethylene (TCE) is a major environmental pollutant. An immunological response is a newlyrecognized mechanism for TCE-induced kidney damage. However, the role of the plasma kallikreinkinin system (KKS) in immune-mediated kidney injury has never been examined. This study aimed to explore the role of the key components of the KKS, i.e. plasma kallikrein (PK), bradykinin (BK) and its receptors B1R and B2R, in TCE-induced kidney injury. A mouse model of skin sensitization was used to explore the mechanism of injury with or without a PK inhibitor PKSI. Kidney function was evaluated by measuring blood urea nitrogen (BUN) and creatinine (Cr) in conjunction with histopathologic characterization. Plasma BK was determined by ELISA; Renal C5b-9 membrane attack complex was evaluated by immunohistochemistry. Expression of BK and PK in the kidney was detected by immunoFuorescence. mRNA and protein levels of B1R and B2R were assessed by real-time qPCR and Western blot. As expected, numerous inflammatory cell inEltration and tubular epithelial cell vacuolar degeneration were observed in TCE-sensitized mice. Moreover, serum BUN and Cr and plasma BK were increased. In addition, deposition of BK, PK and C5b-9 were observed and B1R and B2R mRNA and proteins levels were up-regulated. Pre-treatment with PKSI, a highly selective inhibitor of PK, alleviated TCE-induced renal damage. In addition, PKSI attenuated TCEinduced up-regulation of BK, PK and its receptors and C5b-9. These results provided the first evidence that activation of the KKS contributed to immune-mediated renal injury induced by TCE and also helped to identify the KKS as a potential therapeutic target for mitigating chemical sensitization-induced renal damage.ARTICLE HISTORY

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The Kallikrein–Kinin system

Cited by 48 publications

References 47 publications

Autoimmune Diabetes Is Suppressed by Treatment with Recombinant Human Tissue Kallikrein-1

Autoimmune Diabetes Is Suppressed by Treatment with Recombinant Human Tissue Kallikrein-1

Consumption of Amaranth Induces the Accumulation of the Antioxidant Protein Paraoxonase/Arylesterase 1 and Modulates Dipeptidyl Peptidase IV Activity in Plasma of Streptozotocin-Induced Hyperglycemic Rats

Plasma Kallikrein-Kinin system mediates immune-mediated renal injury in trichloroethylene-sensitized mice

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