Bacterial are known to provoke host defense system via there endotoxins. Endotoxins activate innate immune system by many different pathways, but activation of TLR4 (Tool Like Receptor 4) is one of the key pathway. Activated TLR4 give response by two distinct, but interrelated pathways, naming MyD88 dependent and MyD88 independent pathways. MyD88 dependent pathway proceed via TRF6 and IRAK family leading to activation of NF-κB, which in result initiate expression of inflammatory response genes. While MyD88 independent pathway cause expression of type I IFN, by activation of NF-κB and JNK. In this project, we treat balb/c mice with LPS and use lung to extract RNA and protein at different time point. RNA was undergone sequencing using Helicose tSMS™ sequencer, which is next generation sequencer. Result show up-regulation of H2B isoforms between treated v/s untreated (0 hr after exposure of LPS. Also putative binding site for IRF/STAT was found on all H2B isoforms using GeneACT ®. It was thought that STAT activation via MyD88 independent pathway leads to up-regulation of IRF, which in turns binds to H2B isoforms to increase its expression.
To check our result western blot is performed, whose results found to correlate with that of sequencing data. But how up-regulation of histone adds to host immune system? Histones are known to get digested by many proteases in body and small fragments of histone are proven to have antimicrobial activity.
These histone peptides get attached to invading microbes and make them more prone to host immune system, one way or another. So this suggests how invasion of microbes cause up-regulation of Histones via innate immune system, which might act against them. This study hypothesizes a novel way of response by innate immune system to work on in future.
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|Advisor:||McCaffrey, Timothy A.|
|School:||The George Washington University|
|Department:||Genomics and Bioinformatics|
|School Location:||United States -- District of Columbia|
|Source:||MAI 49/03M, Masters Abstracts International|
|Subjects:||Genetics, Biochemistry, Bioinformatics, Immunology|
|Keywords:||Endotoxin, Histone, IRF, Innate immune system, Sequencing, TLR4|
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