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

Abstract

BACKGROUND The objectives of this study were to determine 1) expression of oral secretory leukocyte protease inhibitor (SLPI) in HIV-infected subjects compared to non-HIV controls, 2) the oral SLPI expression in HIV-infected subjects with ART compared to those without ART, and 3) factors associated with the expression of oral SLPI. METHODS 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. RESULTS One hundred and fifty-seven HIV-infected subjects were enrolled; 99 on ART (age range 23–57 yr, mean 39 yr), 58 not on ART (age range 20–59 yr, mean 34 yr), and 50 non-HIV controls (age range 19–59 yr, mean 36 yr). The most common ART regimen was 2 NRTIs+1 NNRTI. 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. CONCLUSION 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.

Oral innate immunity in HIV infection in HAART era

“…The significant increase in SLPI mRNA expression and protein secretion was dose and time dependent, occurred rapidly after virus contact, did not require productive cellular infection, and was elicited specifically by the external envelope glycoproteins of HIV strains (44). A recent study by Nittayananta et al (43) reported that HIV infection may affect the expression of oral SLPI at both transcriptional and translational levels. The study showed that the expression of oral SLPI mRNA in HIV-infected individuals was increased; however, the levels of SLPI protein in stimulated saliva was decreased (43).…”

“…This finding may indicate that the expression of SLPI is also controlled at the post-transcriptional level, and that HIV infection may alter message translation or interfere with the protein synthesis. In addition, the study reported that CD4 T-cell count and HIV viral load were the factors associated with the oral SLPI expression (43). Thus, HIV infection may impair the function of oral epithelial cells in innate immunity leading to the alterations of the expression of oral SLPI.…”

“…The salivary component has also been shown to be different between those with HAART and without HAART (34). In addition, the expression of oral SLPI has been shown to be affected by the use of HAART (43). A study by Nittayananta et al (43) reported that the levels of SLPI protein in stimulated saliva was decreased in those on short-term HAART compared with those who did not take the medications.…”

“…In addition, the expression of oral SLPI has been shown to be affected by the use of HAART (43). A study by Nittayananta et al (43) reported that the levels of SLPI protein in stimulated saliva was decreased in those on short-term HAART compared with those who did not take the medications. However, the expression of SLPI mRNA did not change significantly (43).…”

SLPI (secretory leukocyte peptidase inhibitor)

“…Also, it has been suggested that a form of cleaved SLPI can reflect the disease activity of patients with allergic rhinitis and asthma (Belkowski et al 2009). It was also been proposed as a biomarker in ovarian and gastric cancer (Devoogdt et al 2009;Cheng et al 2008), or to identify subjects at risk of infections and malignant transformation due to HIV infection (Nittayananta et al 2013). Recently, it was proposed as a biomarker for acute kidney injury after transplantation (Wilflingseder et al 2014).…”