SYSTEMS BIOLOGY AND MOLECULAR PATHWAYS IN CHRONIC INFLAMMATION

Abstract

Chronic inflammation has become one of significant contributors of complex illnesses yet the mechanism to this effect is not very clear at the molecular level.  In this research, a mixed-method systems biology, which involves transcriptomics, proteomics and metabolomics, is utilized to determine what regulatory networks, as well as pathways changes are associated with chronic inflammatory diseases.  Important inflammatory genes, including IL-6, TNF-a, NLRP3 and STAT3, are switched on as revealed by high-throughput RNA sequencing. It was observed that the protein expression also increased as analyzed by ELISA and western blot.  Metabolomic analysis identified gross alterations in the immunometabolic intermediates including succinate, lactate and arachidonic acid. This indicates that the body is shifting to pro-inflammatory energy metabolism.  Principal component analysis and multi-modal hybrid plot succeeded in separating treatment group (treated), sick, and control groups remarkably well. This indicates which signatures of omics are robust and reefficient.  Further, time-resolved expression analysis revealed that cytokine activity decreased in response to treatment, which indicates that the pathway was most likely blocked throughout the duration of study.  The persistence of this disease was associated with pathway enrichment, network centrality analysis, and experimental verification of involvement of NF- 0 B, JAK- STAT, and NLRP3 inflammasome pathways.  The findings can be used to describe the chronic inflammation mechanism and identify certain molecular targets that could be deployed in diagnostics and therapy.  This is the demonstration of the capability of multi-layered systems biology to decipher complex immune system issues and advance precision medicine.