2  Aim and objectives of the study

Lipid mediators such as, leukotrienes, prostaglandins, lipoxins and lipoxygenase metabolites are important constituents of inflammatory process. Of these, 12/15-lipoxygenase and its metabolites were observed prominently in bronchial inflammatory diseases like asthma and bronchitis. Th2 cytokines, IL-4 and IL-13, have been observed to induce the expression of the 12/15-LOX and are also present in bronchial inflammatory conditions. The 12/15-LOX metabolites, especially 15-HETE and 13-HODE, have been observed to function as ligands for nuclear receptor/transcription factor PPARγ. The exact nature of the influence these factors have in the pathogenesis of inflammatory bronchial diseases is not clear. The enzyme has also been implicated in other disorders such as insulin dependent diabetes. In rat β islet cells, novel metabolites of 12/15-LOX, hepoxilins, have been observed though the pathways involved in their biosynthesis are little understood.

1. The aim of the study was to characterise the mechanism of induction of 12/15-LOX expression by IL-4 in lung carcinoma cell line, A549. Experiments were aimed at elucidating the signal transduction pathways involved. Our main focus was on understanding changes occurring in the chromatin structure, especially histone modifications and the interaction between the various transcription factors and co-activators required for the induction of mRNA synthesis.
2. One of the objectives of the study was to determine the role of 12/15-LOX enzyme and its metabolites in the apoptotic process, or cell death observed during bronchial inflammation. In particular, the nature of involvement of PPARγ and the characterisation of the downstream signalling steps leading to apoptosis.
3. The nature of the biosynthetic pathway of hepoxilin was investigated in rat β islet cells. The intrinsic hepoxilin synthase activity of 12/15-LOX was examined along with the regulation of synthesis of hepoxilins.