Salivary Secretory Leukocyte Protease Inhibitor Research Articles

Low Salivary Secretory Leukocyte Protease Inhibitor Levels Are Related to Airway Pseudomonas aeruginosa Infection in Bronchiectasis

Low Salivary Secretory Leukocyte Protease Inhibitor Levels Are Related to Airway Pseudomonas aeruginosa Infection in Bronchiectasis

Salivary secretory leukocyte protease inhibitor levels in patients with stage 3 grade C periodontitis: a comparative cross-sectional study.

Secretory leukocyte protease inhibitor (SLPI) is an anti-protease that protects mucosal tissue integrity owing to its anti-microbial and immunomodulatory properties. This study aimed to investigate SLPI levels in periodontal diseases, and analyze the potential correlation with clinical periodontal parameters. Whole saliva samples were obtained from healthy (n = 24), gingivitis (n = 24) and patients with stage 3 grade C periodontitis (n = 24). SLPI was measured by ELISA and normalized by total protein. Receiver operating characteristics (ROC)curve was used for estimating the area under the curve (AUC). The normalized SLPI levels were significantly reduced in periodontitis compared with gingivitis (4.84-fold) or health (1.83-fold) and negatively correlated with periodontal parameters. The ROC curves showed a good predictor value of the SLPI for differentiation of periodontitis versus health or gingivitis (AUC ≥ 0.80). This study demonstrates that the levels of SLPI are high in periodontal health, further elevated in gingivitis, but eventually decreased in severe periodontitis beyond the former two states. This observation may have broader implications in the context of inflammatory diseases affecting the oral mucosa, as it shows that the bacterial burden is disturbing the homeostatic balances of anti-microbial and anti-protease factors in the oral cavity.

Oral secretory leukocyte protease inhibitor (SLPI): Associations with oropharyngeal cancer and treatment outcome.

BackgroundRates of oropharyngeal cancer (OPC) associated with alcohol & tobacco use have decreased, while human papillomavirus (HPV) associated OPC has increased among men in the US. Secretory leukocyte protease inhibitor (SLPI), detectable in a variety of secretions, has been implicated in cancers of the head and neck, associated with tumor progression and anti-viral activity. Using the recently verified oral gargle specimen, this study aimed to assess the association of salivary SLPI expression with risk of OPC and response to treatment.MethodsA case-control study design compared levels of salivary SLPI among OPC cases to age and tobacco smoking matched healthy controls. Oral HPV DNA and SLPI was quantified from oral gargle specimens. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for associations of oral SLPI and risk of OPC and treatment outcomes.ResultsIn crude and adjusted analyses of 96 OPC cases and 97 age- and smoking-matched controls, OPC was not significantly associated with oral gargle SLPI levels. Among cases, oral SLPI was associated with tonsillectomy (p = 0.018) and among controls oral SLPI was associated with HPV in the oral gargle (p = 0.008). Higher concentrations of SLPI was significantly associated with increased odds of incomplete treatment response (T2: OR: 12.39; 95% CI: 1.44–106.72; T3: OR: 9.86; 95% CI: 1.13–85.90) among all cases, but not among P16+ cases.ConclusionsSalivary SLPI was not associated with OPC risk but was associated with higher odds of an incomplete treatment response.

Secretory Leukocyte Protease Inhibitor in Oral Potentially Malignant Disorders and Oral Squamous Cell Carcinoma

Abstract Objectives: Secretory leukocyte protease inhibitor (SLPI) is a protein found in body fluids and implicated as a prognostic factor in many cancers. There is limited research regarding serum and salivary SLPI in oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC). Materials and Methods: A total of 90 participants were included in the study; of which 30 formed the control group, 30 included participants with OPMD, and 30 included participants with OSCC. Serum and salivary levels of SLPI were estimated using enzyme-linked immunosorbent assay. Results: Serum levels of SLPI showed progressive increase in potentially malignant disorders and SCC patients when compared with controls, while salivary levels were increased in both OPMD and OSCC groups as compared to controls. However, the difference between groups was not statistically significant (P < 0.05). Conclusion: The above results suggest that increase in SLPI levels in the serum may have a role in indicating progression of OPMD to OSCC.

Expression of Salivary Secretory Leukocyte Protease Inhibitor in Smokers, Leukoplakia and OSCC

Expression of Salivary Secretory Leukocyte Protease Inhibitor in Smokers, Leukoplakia and OSCC

Distribution and factors associated with salivary secretory leukocyte protease inhibitor concentrations.

This cross-sectional study examined the distribution and correlates of salivary secretory leukocyte protease inhibitor (SLPI) concentrations within a multinational cohort of men. Extracellular SLPI was measured in oral gargle cell supernatants of 378 men from three countries using an ELISA-based assay. Risk factor data were collected by a questionnaire. Factors associated with SLPI were assessed using linear and logistic regression for continuous and categorical SLPI, respectively. Among men aged 18-73years, the median SLPI concentration was 492.0ngml-1 (range: 2.3-1919.9). In multivariable modeling, men in Brazil and younger men (18-30years) were more likely to have higher levels of SLPI [adjusted odds ratio (aOR) 3.84; 95% confidence interval (CI): 1.94-7.59, and aOR 3.84; 95% CI: 1.98-7.43, respectively]. Men with a self-reported sexually transmitted diseases diagnosis in the past 6months were more likely to have higher SLPI levels (aOR 2.98; 95% CI: 1.1-7.83) and men reporting bleeding/swollen gums were less likely to have higher SLPI (aOR 0.34; 95% CI: 0.15-0.79). Similar results were observed for linear regression models. Secretory leukocyte protease inhibitor concentrations varied significantly by country and decreased with increasing age. The interaction between SLPI, modifiable factors, and oral infections that influence cancer risk warrants further investigation.

Salivary secretory leukocyte protease inhibitor (SLPI) and head and neck cancer: The Cancer Prevention Study II Nutrition Cohort

Secretory leukocyte protease inhibitor (SLPI) is an innate-immunity protein displaying antimicrobial and anti-inflammatory properties that is found in high concentrations in saliva. The role of extracellular salivary SLPI in head and neck squamous cell carcinoma (HNSCC) remains unclear. Thus, we aimed to evaluate the association between SLPI and HNSCC risk in the Cancer Prevention Study II Nutrition Cohort. Among 53,180 men and women with no history of cancer who provided an oral rinse between 2001 and 2002, 60 were subsequently diagnosed with incident HNSCC between specimen collection and June 2009. In this nested case-control study, archived oral supernatants were evaluated using the Human SLPI Quantikine ELISA Kit for all 60 cases and 180 controls individually matched on gender, race, date of birth, and date of oral rinse collection. Conditional logistic regression was used to estimate HNSCC risk. Overall, pre-diagnostic salivary SLPI was associated with a non-statistically significant higher risk of HNSCC (OR=1.6, 95% CI=0.9-3.0). Among never smokers, high SLPI was associated with a non-statistically significant lower risk (OR=0.5, 95% CI=0.1-1.9), whereas among ever smokers, high SLPI was associated with a statistically significant higher risk (OR=2.1, 95% CI=1.0-4.3) of HNSCC, compared to low SLPI. While results from this study suggest that higher concentrations of salivary SLPI might increase the risk of HNSCC among ever smokers, more research is needed to verify these findings and define the mechanisms by which SLPI and smoking influence the etiology of HNSCC.

Estimation and comparison of salivary secretory leukocyte protease inhibitor in human immunodeficiency virus patients and healthy individuals

Aim:Transmission of human immunodeficiency virus (HIV) in the oral cavity is a rare event, despite detectable virus in saliva and oropharyngeal tissues of infected persons, unlike other mucosal sites. Secretory leukocyte protease inhibitor (SLPI) has been suggested as the main soluble factor responsible for the HIV inhibitory effect of saliva. The study was designed to estimate and compare the salivary SLPI levels in HIV patients and healthy controls. Furthermore, the relationship between salivary SLPI levels and disease severity was also investigated.Materials and Methods:Unstimulated whole saliva specimens were collected from 60 HIV-infected and 20 healthy subjects. Disease severity was determined by CD4 count in HIV subjects, who were divided into two groups: ≥200 cells/μL (n = 30) and < 200 cells/μL n = 30. Salivary SLPI levels were determined by enzyme-linked immunosorbent assay.Results:Numerically higher SLPI levels were observed in HIV subjects 193.342 ng/mL vs. 190.587 ng/mL; P = 0.517. A nonsignificant negative correlation was noted between CD4 counts and SLPI levels r = −0.037, P = 0.781.Conclusion:The salivary anti-HIV factor, SLPI, is not only preserved in HIV infection but its concentration may even get enhanced in the infection. However, the clinical significance of SLPI levels and disease severity should be investigated further with a larger sample of patients.

Quantification of secretory leukocyte protease inhibitor (SLPI) in oral gargle specimens collected using mouthwash

BackgroundSecretory leukocyte protease inhibitor (SLPI) is an innate immunity-associated protein known to inhibit HIV transmission, and is thought to inhibit a variety of infectious agents, including human papillomaviruses (HPVs). We aimed to optimize an established ELISA-based SLPI quantification assay for use with oral gargle specimens collected using mouthwash, and to assess preliminary associations with age, smoking status, and alcohol intake. MethodsOral gargle supernatants from 50 individuals were used to optimize the Human SLPI Quantikine ELISA Kit. Sample suitability was assessed and quality control analyses were conducted. ResultsSalivary SLPI was successfully recovered from oral gargles with low intra-assay and high inter-individual variability. Initial measurements showed that salivary SLPI varied considerably across individuals, and that SLPI was inversely associated with age. ConclusionsThis optimized assay can be used to examine the role of SLPI in the acquisition of oral HPV and other infections.

Expression of oral secretory leukocyte protease inhibitor in HIV‐infected subjects with long‐term use of antiretroviral therapy

The objectives of this study were to determine (i) the expression of oral secretory leukocyte protease inhibitor (SLPI) in HIV-infected subjects compared with non-HIV controls, (ii) the oral SLPI expression in HIV-infected subjects with antiretroviral therapy (ART) compared with those without ART, and (iii) factors associated with the expression of oral SLPI. Oral tissues and samples of both un-stimulated and stimulated saliva were collected from HIV-infected subjects with and without ART, and non-HIV individuals. The expression of SLPI mRNA in the tissue was determined by quantitative real-time PCR. Salivary SLPI protein was detected using ELISA. Chi-square test and logistic regression analysis were performed to determine the association between HIV/ART status and the expression of oral SLPI. One hundred and fifty-seven HIV-infected subjects were enrolled: 99 on ART (age range, 23-57years; mean, 39years), 58 not on ART (age range, 20-59years; mean, 34years), and 50 non-HIV controls (age range, 19-59years; mean, 36years). The most common ART regimen was 2NRTIs+1NNRTI. The expression of oral SLPI in stimulated saliva was significantly decreased with HIV infection (P<0.001). The expression was also significantly different with respect to ART use (P=0.007). Smoking, CD4(+) cell count, and HIV viral load were the factors associated with the oral SLPI expression. The expression of oral SLPI is altered by HIV infection and use of ART. Thus, oral SLPI may be the useful biomarker to identify subjects at risk of infections and malignant transformation due to HIV infection and long-term ART.

Salivary secretory leukocyte protease inhibitor increases in HIV infection.

Secretory leukocyte protease inhibitor (SLPI) is an antimicrobial protein found in saliva and having anti-HIV activity. The concentrations of SLPI in parotid and submandibular/sublingual (SMSL) saliva were determined in an HIV(+) population and compared with uninfected controls. The effect of highly active antiretroviral therapy (HAART) on the concentrations in saliva was determined. Stimulated parotid and SMSL saliva was collected from 65 HIV(+) patients and 19 healthy controls. Flow rates, total protein and SLPI concentrations were determined as well as the effect of HAART on these measurements. Mean flow rates were reduced for parotid (64%) and SMSL (44%) saliva of HIV(+) patients. Flow rate reductions were unaffected by HAART. Total protein concentration in HIV(+) parotid saliva was increased 56%; patients on HAART had higher concentrations than control. For both groups, SLPI concentrations of SMSL saliva were twice that of parotid saliva. For HIV(+) patients SLPI concentrations of both saliva types were 70% greater than control; the increase in parotid saliva was greater for those taking HAART. For each saliva type, the secretory rate and specific SLPI protein concentration were not different between the groups. Patients with low CD4(+) counts had greater SLPI concentrations in parotid saliva than control. There was a negative correlation between CD4(+) counts and the SLPI concentration of parotid saliva. Salivary flow rate is decreased and the concentration of SLPI is increased in the presence of HIV infection. SLPI concentration in parotid and SMSL saliva is greater with HAART.

Salivary secretory leukocyte protease inhibitor and oral candidiasis in human immunodeficiency virus type 1-infected persons.

Oropharyngeal candidiasis, typically caused by Candida albicans, is the most common oral disease associated with human immunodeficiency virus type 1 (HIV-1) infection. Secretory leukocyte protease inhibitor (SLPI), a 12-kDa antiprotease, suppresses the growth of C. albicans in vitro. To determine whether the mucosal protein plays a role in protecting oral tissues against fungal infection, we conducted a cross-sectional study investigating the oral and systemic health and salivary SLPI levels in 91 dentate HIV-1-infected adults receiving medical care in the southeastern United States. Participants with a self-reported history of clinical oropharyngeal candidiasis during the previous 2 years constituted the test group (n = 52), while the comparison group (n = 39) had no oropharyngeal candidiasis during that period. Data collected from medical records, oral examination, and SLPI enzyme-linked immunosorbent assay quantitation of whole saliva were analyzed by t test, analysis of variance, linear regression, and unconditional logistic regression. The test group had a significantly higher mean salivary SLPI level than the comparison group (1.9 microg/ml versus 1.1 microg/ml, P < 0.05). Linear regression modeling identified CD4 cell count and history of oropharyngeal candidiasis as key predictors of salivary SLPI and revealed a significant interaction (P < 0.05) between immunosuppression (CD4 cell count below 200 cells/ microl) and positive history of oropharyngeal candidiasis in predicting salivary SLPI level. By logistic regression modeling, a salivary SLPI level exceeding 2.1 microg/ml, low CD4 count, antiretroviral monotherapy, and smoking were key predictors of oropharyngeal candidiasis. These data support a key role for SLPI in the oral mucosal defense against C. albicans. The antimicrobial mucosal protein may serve as an indicator of previous oropharyngeal candidiasis infection among immunosuppressed persons.

Salivary secretory leukocyte protease inhibitor is associated with reduced transmission of human immunodeficiency virus type 1 through breast milk.

Secretory leukocyte protease inhibitor (SLPI), a protein found in saliva, breast milk, and genital secretions, is capable of inhibiting human immunodeficiency virus (HIV) type 1 in vitro. The aim of this study was to determine whether SLPI in infant saliva provides protection against mother-to-child HIV-1 transmission. In total, 602 saliva specimens were collected from 188 infants at birth and at ages 1, 3, and 6 months. Infants' median salivary SLPI concentrations were higher at birth than at 6 months (341 vs. 219 ng/mL; P=.001). There was no association between SLPI concentration and HIV-1 transmission overall. However, among 122 breast-fed infants who were HIV-1 uninfected at 1 month, higher salivary SLPI levels were associated with a decreased risk of HIV-1 transmission through breast milk (hazard ratio, 0.5; 95% confidence interval, 0.3-0.9; P=.03). These results suggest that SLPI plays an important role in reducing HIV-1 transmission through breast milk.

Identification of a novel secretory leukocyte protease inhibitor-binding protein involved in membrane phospholipid movement

Previous studies have suggested that human salivary secretory leukocyte protease inhibitor (SLPI) inhibits HIV-1 by binding to a host cell surface protein of unknown identity. Using the yeast two-hybrid assay, we identified a gene sequence encoding a novel SLPI-binding protein (SLPI-BP). The 1.5-kb cDNA encodes a 318-amino acid protein with a predicted transmembrane segment near the C-terminus. Sequence analysis revealed that SLPI-BP is the human scramblase protein that is involved in the movement of membrane phospholipids. Co-expression of SLPI and SLPI-BP followed by an S-protein pulldown assay confirmed the specific interaction between these two proteins. Our data represent the first report for the identity of SLPI-BP.