Page 96 - CSIR-IGIB Annual Report 2020-21
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identified glycoprotein was able to activate decremental effect of diesel exhaust on lung
passively sensitized basophils and showed cross- health and increase in pro-inflammatory
reactivity with common edible legume proteins cytokines. Therefore, further analysis was focused
such as peanut, kidney bean, soy, black gram, and on strengthening our previous hypothesis i.e.,
lima bean. Dendritic cells possess mannose exposure to diesel exhaust leads to pulmonary
receptor which binds various glycoprotein fibrosis and deciphering the molecular pathway
allergens playing an important role in allergen involved in DE-induced lung fibrosis. We,
uptake. The interaction of 35 kDa allergen was therefore, analysed the activation of TGF-β
studied with bone-marrow derived dendritic cells signaling activation and found significant increase
(Dendritic cells). The glycoprotein was tagged with in expression of smad-3 & P-smad3 as compared
Cy5 dye, and the signal was analysed by flow to control mice using western blot. Further, we
cytometry and microscopy studies. The 35kDa analysed mechanism involved in DE-induced lung
protein enters the Dendritic cells via mannose fibrosis and found regulation of EMT (Epithelial to
receptor and downregulates the IDO (enzyme of Mesenchymal transition). We observed significant
tryptophan metabolism). Studies reports strong increase in mesenchymal maker i.e., Vimentin and
evidence of the role of IDO in tolerance induction significant decrease in epithelial maker i.e., E-
during immunotherapy regimen. Furthermore, cadherin via western blot analysis. EMT and
data from patients with pollinosis, asthma and pulmonary fibrosis are the known comorbidity of
allergy correlate with altered levels of IDO lung cancer progression involving varied
suggesting the role of IDO pathway in allergic pathways. Further, microarray was used to
inflammation. analyse the altered pathways involved in lung
cancer progression. This data suggested 30
Diesel exhaust and its impact on respiratory health differentially expressed miRNA. Among these
Exposure to air pollution has shown deleterious miRNAs, mmu-miR-133b-3p expression was
effect on lung health and is associated with airway significantly downregulated in miRNA microarray
obstruction. Diesel engines being predominantly analysis. Further, target prediction of mmu-miR-
used in heavy transportation account for a major 133b-3p suggested 371 consensus gene using
increase in ambient NOx and particulate matter different bioinformatic tools. DAVID analysis of
(PM). Long term exposure of diesel exhaust these miRNA revealed 16 significantly enriched
particulate has suggested increased lung pathways in which we are working on the Hippo
inflammation and tissue remodeling. Also, signaling pathway and MAPK signaling pathway.
increased exacerbation of emphysema and The future studies involve target genes validation
asthma have been associated with diesel particle in pathways
exposure. Our earlier data have shown
Annual Report 2020-21 93
