Secretory leukocyte protease inhibitor (SLPI), a multifunctional protein in the host defense response

Majchrzak-Gorecka, Monika; Majewski, Paweł; Grygier, Beata; Murzyn, Krzysztof; Cichy, Joanna

doi:10.1016/j.cytogfr.2015.12.001

Cited by 105 publications

(93 citation statements)

References 114 publications

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“…Apart from its anti-inflammatory functions, SLPI may control the growth of bacteria and fungi in a charge-dependent manner www.nature.com/scientificreports www.nature.com/scientificreports/ similar to other cationic peptides, such as defensins by disrupting microbial membranes 39,40 . By its immunomodulatory, anti-proteolytic, and anti-microbial action, SLPI functions as a regulator of innate and adaptive host defense 8,41 .…”

Section: Discussionmentioning

confidence: 99%

SLPI - a Biomarker of Acute Kidney Injury after Open and Endovascular Thoracoabdominal Aortic Aneurysm (TAAA) Repair

Averdunk

Rückbeil

Zarbock

et al. 2020

Sci Rep

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Acute kidney injury (AKi) is a relevant complication following thoracoabdominal aortic aneurysm repair (tAAA). Biomarkers, such as secretory leucocyte peptidase inhibitor (SLpi), may enable a more accurate diagnosis. in this study, we tested if SLpi measured in serum is an appropriate biomarker of AKi after TAAA repair. In a prospective observational single-center study including 33 patients (51.5% women, mean age 63.0 ± 16.2 years) undergoing open and endovascular aortic aneurysm repair in 2017, SLPI was measured peri-operatively (until 72 h after surgery). After surgery, the postoperative complications AKI, as defined according to the KDIGO diagnostic criteria, sepsis, death, MACE (major cardiovascular events) and, pneumonia were assessed. in a subgroup analysis, patients with preexisting kidney disease were excluded. Of 33 patients, 51.5% (n = 17) of patients developed AKI. Twelve hours after admission to the intensive care unit (ICU), SLPI serum levels were significantly increased in patients who developed AKI. Multivariable logistic regression revealed a significant association between SLPI 12 hours after admission to ICU and AKI (P = 0.0181, OR = 1.055, 95% CI = 1.009-1.103). The sensitivity of SLPI for AKI prediction was 76.47% (95% CI = 50.1-93.2) and the specificity was 87.5% (95% CI = 61.7-98.4) with an AUC = 0.838 (95% CI = 0.7-0.976) for an optimal cut-off 70.03 ng/ml 12 hours after surgery. in patients without pre-existing impaired renal function, an improved diagnostic quality of SLpi for AKI was observed (Sensitivities of 45.45-91.67%, Specificities of 77.7-100%, AUC = 0.716-0.932). there was no association between perioperative SLpi and the incidence of sepsis, death, MAce (major cardiovascular events), pneumonia. this study suggests that SLpi might be a post-operative biomarker of AKi after tAAA repair, with a superior diagnostic accuracy for patients without preexisting impaired renal function.Open and endovascular repair of thoracoabdominal aortic aneurysm (TAAA) is related to a high risk of postoperative complications. With an incidence ranging between 13 and 42%, acute kidney injury (AKI) is one of the most common complications and closely associated with increased mortality and cardiovascular morbidity 1-3 . The early detection of impaired kidney function and other organ dysfunctions may enable an immediate start of specific treatment bundles. The diagnosis of AKI is mainly based on patients' urine output and serum creatinine levels. Serum creatinine is an established, yet controversial biomarker due to its delayed increase and low sensitivity for the detection of an impaired kidney function 4-6 . In this context, the necessity of clinically available early and reliable biomarkers of AKI becomes evident.Secretory leucocyte peptidase inhibitor (SLPI) is a protease inhibitor and regulator of innate and adaptive immunity 7 . It is synthesized predominantly in immune and epithelial cells of mucosal surfaces, such as the pancreas and kidney 8 . Elevated serum SLPI levels have been observed in acu...

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Section: Discussionmentioning

confidence: 99%

SLPI - a Biomarker of Acute Kidney Injury after Open and Endovascular Thoracoabdominal Aortic Aneurysm (TAAA) Repair

Averdunk

Rückbeil

Zarbock

et al. 2020

Sci Rep

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“…Salivary glands, epithelial cells, and oral cavity-recruited neutrophils produce over 45 AMPs that are detected in saliva and gingival crevicular fluid. These include cathelicidins (LL37), α-defensins, β-defensins, histatins, and secretory leukocyte protease inhibitor (SLPI) (23–26). Because AMPs utilize different strategies to restrict microbial growth (24, 27), their diversity may be important for independently controlling the load, composition, and location of microbial communities in the oral cavity and for maintaining oral homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial and Attractant Roles for Chemerin in the Oral Cavity during Inflammatory Gum Disease

et al. 2017

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Periodontal inflammation is one of the most common chronic inflammatory conditions in humans. Despite recent advances in identifying and characterizing oral microbiota dysbiosis in the pathogenesis of gum disease, just how host factors maintain a healthy homeostatic oral microbial community or prevent the development of a pathogenic oral microbiota remains poorly understood. An important determinant of microbiota fate is local antimicrobial proteins. Here, we report that chemoattractant protein chemerin, which we recently identified as a potent endogenous antimicrobial agent in body barriers such as the skin, is present in the oral cavity under homeostatic and inflammatory conditions. Chemerin and a chemerin-derived antimicrobial peptide are bactericidal against select bacteria strategically positioned in dental biofilm. Gingival crevicular samples from patients with gingivitis but not periodontitis contain abundant bioactive chemerin capable of inducing CMKLR1-dependent leukocyte migration. Gingipains secreted by the periodontopathogen P. gingivalis inactivate chemerin. Together, these data suggest that as an antimicrobial agent and leukocyte chemoattractant, chemerin likely contributes to antimicrobial immune defense in the oral cavity.

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“…Excitingly, we found that Bldesin had apparent inhibitory activities on serine protease chymotrypsin and elastase, and 2500 nM Bldesin inhibited over 40% chymotrypsin activity. These results indicated that pathogenic fungus‐derived defensin Bldesin is an important serine protease inhibitor and might play potential roles in the defense of host serine protease system …”

Section: Resultsmentioning

confidence: 84%

“…Different from soil‐derived fungus defensin Plectasin, pathogenic fungus‐derived defensin Bldesin might play potential functional roles in the fungus‐host interactions, such as its potential functional roles in the defense of environmental bacteria and the Kv1.3 channel‐associated host immunity. As we know, serine protease also played important roles in the host defense system . So, we further tested the effect of defensin Bldesin on host serine protease system.…”

Section: Resultsmentioning

confidence: 99%

Bldesin, the first functionally characterized pathogenic fungus defensin with Kv1.3 channel and chymotrypsin inhibitory activities

Luo

Zhu

et al. 2018

J Biochem & Molecular Tox

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Fungus defensin is a kind of important natural peptide resource, such as plectasin from the soil fungus Pseudoplectania nigrella with potential application in the antimicrobial peptide lead drug discovery. Here, a fungus defensin named Bldesin with Kv1.3 channel and serine protease inhibitory activities was first explored. By GST-Bldesin fusion expression and enterokinase cleaving strategy, recombinant Bldesin was obtained successfully. Antimicrobial assays showed that Bldesin had potent activity against Grampositive Staphylococcus aureus, but had no effect on Gram-negative Escherichia coli.Electrophysiological experiments showed that Bldesin had Kv1.3 channel inhibitory activity. Serine protease inhibitory associated experiments showed that Bldesin had unique chymotrypsin protease inhibitory, elastase protease inhibitory, and serine protease-associated coagulation inhibitory activities. To the best of our knowledge, Bldesin is the first functionally characterized pathogenic fungus defensin with Kv1.3 channel and chymotrypsin inhibitory activities and highlighted novel pharmacological effects of fungus-derived defensin peptides.

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Secretory leukocyte protease inhibitor (SLPI), a multifunctional protein in the host defense response

Cited by 105 publications

References 114 publications

SLPI - a Biomarker of Acute Kidney Injury after Open and Endovascular Thoracoabdominal Aortic Aneurysm (TAAA) Repair

SLPI - a Biomarker of Acute Kidney Injury after Open and Endovascular Thoracoabdominal Aortic Aneurysm (TAAA) Repair

Antimicrobial and Attractant Roles for Chemerin in the Oral Cavity during Inflammatory Gum Disease

Bldesin, the first functionally characterized pathogenic fungus defensin with Kv1.3 channel and chymotrypsin inhibitory activities

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