A-257 Association Between Matrix Metalloproteinase-3 and its Post-Transcriptional Regulator miR-17-5p in the Pathogenesis of Tuberculous Meningitis Patients

Abstract

Abstract Background Tuberculosis, a communicable disease caused by Mycobacterium tuberculosis is one of the top 10 causes of death worldwide. Tuberculous meningitis (TBM), an extra-pulmonary central nervous system tuberculosis is the most severe form with maximum mortality. To combat the complications of disease, host immune response gets activated which initially protects the host but later an exaggerated response leads to aggravation of the disease. This causes tremendous neuroinflammation which further increases the complications of the disease. Matrix metalloproteinase (MMPs) like MMP-9, 2 and 3 are known to cause damage to the blood brain barrier and have a role in the pathogenesis of disease particularly increasing the neuroinflammation. MMPs are regulated at post-transcriptional level by microRNAs (miRNA) that alter their levels by targeting various genes. Based on available literature we found miR-17-5p to be a key regulator of MMP3. In this study, we assessed the levels of MMP3 and its post-transcriptional regulator miR-17-5p in the cerebrospinal fluid (CSF) of TBM patients, healthy controls (HC) and non-infectious neuroinflammatory disease patients (NID). Methods In this study, 100 TBM patients were recruited based on the Lancet scoring system and CSF samples were collected. For NID control group, 25 patients with other non-infectious neuroinflammatory diseases like Guillain-Barre syndrome, multiple sclerosis were recruited. Twenty five HC CSF samples were collected from patients undergoing spinal anaesthesia for any lower limb surgery. The samples were stored at −80°C and processed when required for ELISA and quantitative real time PCR. Results We found a significant increase in levels of median MMP3 levels in the CSF of TBM patients compared to HC group (2.719 ng/ml vs 1.696 ng/ml). The MMP3 levels were also significantly elevated in the NID control group as compared to HC group (3.116 ng/ml vs 1.696 ng/ml). A stagewise comparison in TBM group showed an increase in levels of MMP3 with respect to HC but within stages results were comparable. The expression of MMP3 regulator miR-17-5p showed an upregulation in the CSF of TBM group as compared to NID and HC group. Conclusion An increase in levels of MMP3 was observed in both TBM and NID group which infers that MMP3 might have a role in neuroinflammation in neurological conditions. In our study groups we did not find any relation between miR-17-5p expression and MMP3 levels, indicating that there might be some other regulatory pathway altering the levels of MMP3 in neurological conditions. Hence, further studies can be done to highlight the explicit role of MMP3 in neuroinflammation which can then be targeted therapeutically to relieve the associated complications.