Nonstructural protein-1 (NS1) of dengue virus type-2 differentially stimulate expressions of matrix metalloproteinases in monocytes: protective effect of paracetamol

• Published in: International immunopharmacology 2019-08, Vol.73, p.270-279
• Main Authors: Niranjan, Rituraj, Sumitha, M.K., Sankari, Thirumal, Muthukumaravel, Subramanian, Jambulingam, Purushothaman
• Format: Article
• Language: English
• Subjects: Acetaminophen - pharmacology; Analgesics; Antigens; Cell morphology; Cell viability; Collagenase 3; Cytokines; Cytokines - metabolism; Cytology; Dengue; Dengue fever; Dengue viral disease; Enzyme-linked immunosorbent assay; Exposure; Fever; Gelatinase A; Gelatinase B; Gene expression; Genes; Humans; Interleukin 10; Interleukin 15; Interleukin 4; Interleukin 6; Matrix metalloproteinase; Matrix metalloproteinases; Matrix Metalloproteinases - genetics; Metalloproteinase; Microscopy; Monocytes; Monocytes - drug effects; Monocytes - metabolism; Morphology; Neutrophil collagenase; Nonstructural protein-1; Paracetamol; Pathogenesis; Protective Agents - pharmacology; Proteins; Reagents; RNA, Messenger - metabolism; Stromelysin 2; THP-1 Cells; Tumor necrosis factor-α; Vector-borne diseases; Viral diseases; Viral Nonstructural Proteins - pharmacology; Viruses
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2019.05.022

Dengue fever is a re-emerging viral disease and affects millions of population worldwide. Monocytes are involved in dengue viral disease, however, their exact role is still not clear. In the present study, we investigated, the effect of NS1 antigen of dengue virus and paracetamol on THP-1 monocytes associated to expressions of matrix metalloproteinases (MMPs) and cytokine release. Assessment of cell morphology by bright field microscopy, cell viability by MTT assay, protein estimation by Bradford reagent were done in cells exposed to NS1 antigen in the presence and absence of paracetamol. Cytokines estimations were done by ELISA. Expression profile of matrix metalloproteinase genes was done using real-time PCR and reverse-transcriptase PCR. NS1 exposure of THP-1 monocytes cells, changed their cell morphology and activated them for release of proteins in 24 h. Expressions of MMP-2, MMP-8, MMP-9 and MMP-14 genes were upregulated by NS1 exposure. Further, exposure of NS1 to THP-1 monocytes cells increased expression profile of MMP-10 and MMP-13 genes to a lesser extent. Treatment with paracetamol (1 mg/ml and 2 mg/ml), significantly down-regulated the expression profile of MMP-2, MMP-8, MMP-9 and 14 in dose dependent manner. NS1 exposure also increased the release of cytokines IL-4, IL-6, and IL-10 but decreased the release of TNF-α and IL-15. Interestingly, paracetamol reversed NS1 induced changes in the release of these cytokine in dose dependent manner. Monocytes mediated expression of MMPs participates in the development of dengue pathogenesis in the severe cases of disease and paracetamol may have a protective effect in dengue viral disease. •We highlight the role of monocytes to carry overexpressed matrix metalloproteinases in the case of dengue shock syndrome.•NS1 exposure to monocytes, significantly upregulate expression profiles of MMP-2 and MMP-14 which may be responsible for vascular permeability and thus development of dengue shock syndrome.•Paracetamol has significantly reversed the expression profiles of MMP-2 and MMP-14 showing protective effects.•Further, paracetamol reversed, NS1 induced release of cytokines IL-6, IL10, IL-4, in dose dependent manner.•NS1 induced decrease in TNF-and IL-15 was also reversed by paracetamol.