Research Projects

Tumor necrosis factor like weak inducer of apoptosis (TWEAK) is a pleiotropic and multifunctional cytokine that regulates inflammatory pathways by inducing multiple cellular responses depending on the cell type and its micro-environment. TWEAK exerts its biological activity via binding on its sole and cognate Trans membrane receptor, fibroblast factor-inducible 14 (Fn14). Soluble TWEAK is regarded as the main active form. TWEAK is an inflammatory cytokine primarily synthesized from the immune cells including macrophages. One study recently shown that increased TWEAK level in serum of multiple sclerosis patients (MS), in relation to disease severity and depicted TWEAK as a promising neuroinflammation serum marker in MS patients. Recently, we had collected clinical sputum samples from the gold stage III COPD patients and performed western blotting and ELISA in sputum samples. Our result showed a significant increase in TWEAK level in sputum samples compared to healthy controls. (Figures are attached in preliminary results). In addition, our lab established the elastase and cigarette smoke extract-induced in vitro and in vivo COPD model in which we have checked the level of TWEAK by performing ELISA, western blotting and RT-PCR. (Figures are attached in preliminary results). Increased level of TWEAK was observed in emphysematous COPD lungs as well as in in vitro CSE-induced A549 cells. mRNA level of TWEAK and its sole receptor fibroblast inducible factor-14 (Fn14) was up regulated in elastase-induced lungs Based on these results we have modelled our hypothesis Hypothesis Our hypothesis based on preliminary data and literature survey is as follows i) TWEAK-FN14 axis promotes pulmonary inflammation and cardiovascular irregularities in COPD and blocking this pathway could be a potential therapeutic strategy to reduce inflammation and remodeling of lung-cardiovascular tissues. ii) TWEAK might act as a therapeutic target as well a marker of severity in clinical condition of COPD. Study Objectives a) To decipher the role of TWEAK in COPD associated pulmonary inflammation and tissue remodeling. b) To study the role TWEAK-Fn14 axis in COPD associated cardiac complication. c) To evaluate TWEAK-Fn14 axis in clinical condition (serum or sputum) of COPD patients with reduced lung function and having pulmonary hypertension. Expected output- 1. TWEAK might act as a therapeutic target for COPD and associated pulmonary hypertension. 2. Sputum TWEAK might act as a clinical severity marker for COPD and associated pulmonary hypertension