RNA-seq Based Transcriptome Analysis Of Inflammatory Mouse Lung And Brain Tissues

The viral infections are generally specific to organs;however,some viruses affect multiple organs simultaneously and cause inflammatory diseases.The viral infections of the respiratory and central nervous system(CNS)are the most crucial problems in public health.Usually,some known neurotropic viruses including measles virus and herpes virus among others are responsible for CNS pathologies.However,some respiratory viruses including human respiratory syncytial virus,the influenza virus,the coronavirus and the human metapneumovirus have placed themselves as relevant agents for CNS pathologies.The comparative effects or mechanisms of inflammation in different organs upon the same virus,which can infect multiple tissues,are critical issues of immunology and have to be explored yet.Therefore,we designed this study to find out the mechanisms of differential tissue inflammation between the brain and lung tissues of mouse upon viral mimic treatment.We challenged mice with the viral dsRNA analog polyinosinic acid-polycytidylic acid(poly(I:C))to outline the organ based molecular mechanisms of inflammation.We found differential inflammatory conditions in the brain and lung tissues through quantification of cytokine Il-1? and Tnf-?.We performed transcriptome,protein-interaction and Interferome analysis of inflammatory mouse lung and brain tissues and many other subsequent experiments to outline the reasons behind the differential inflammatory conditions.We identified 629 differentially expressed genes(DEGs)in lung and 137 DEGs in brain tissue with a few overlapping genes.Most of those DEGs were interferon-stimulated genes(ISGs).DEGs of both brain and lung tissues are critically involved in several GO-term including cell adhesion,inflammation,defense response to the virus and innate immunity.The inflammatory effects of viral mimic are higher in the lung than that of the brain tissues in term of the number of DEGs and ISGs.We identified 29 and 14 immune-related hub genes in the lung and brain tissues respectively through the association of protein interactions and signaling pathways.The top five immune-related hub genes in the lung tissues are Itgam,Il-1?,Il-7,Cdkn1 a,and Myc and in the brain tissues are Irf7,Oas2,Ifit1,Isg15,and Rsad2.Besides these hub genes,different ISGs including viral nucleic acid receptor 2'-5'-oligoadenylate synthetase(OAS)associated with inflammation and immune responses and their expression is some extent tissue-specific.In addition,the sequence-specific viral and bacterial RNA receptor Tlr13 upregulation in poly(I:C)stimulated mouse lungs and its interactions with many other inflammation regulatory proteins reflecting its critical roles to regulate lung inflammatory responses.Interestingly Rpl29,a ribosome protein,and cell surface heparin-binding protein is upregulated in the brain and downregulated in the lung.Inhibition of RPL29 with siRNA results in higher expression of the inflammatory cytokines IL-1? and TNF-?.For the first time,we confirmed that the Rpl29 is involved in inflammation as an anti-inflammatory molecule.Its tissue-specific and different expression regulates differential inflammation in lung and brain tissues in response to viral mimic.MiR22 can control many physiological events including inflammation through posttranslational gene regulation.MiR22 has shown different expression in the viral mimic treated lung and brain tissues and in different cell lines.Rpl29 and miR22 show positive co-expression in both tissues.Our study revealed that Rpl29 regulates miR22 expression in different tissues through modulation of Fos-B and c-Fos.In summary,our study suggests that different expression of Rpl29 might have roles on the organ-specific inflammatory responses along with different hub genes,Tlr13,miR22,and ISGs.Rpl29 can also regulate the expression of miR22 in different tissues.We believe that the findings of this study would be beneficial to explore new insights about tissue-specific inflammation and immunity.