期刊
MOLECULAR IMMUNOLOGY
卷 151, 期 -, 页码 70-83出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2022.08.006
关键词
Inflammatory cytokines; Oxidative stress-mediated inflammation; Chronic obstructive pulmonary disease; Lung cancer; CD4+T cells
Dysregulated inflammatory response plays a crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and Non-Small cell lung cancer (NSCLC). This research aims to uncover the link between alterations in inflammatory cytokine levels and disease progression in CD4+T cells of patients suffering from COPD and lung cancer. The findings highlight the need for epigenetic therapy for these debilitating lung diseases.
Dysregulated inflammatory response plays a crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and Non-Small cell lung cancer (NSCLC). Hence, the purpose of this research is to uncover the link between alterations in inflammatory cytokine levels and disease progression in CD4+T cells of patients suffering from COPD and lung cancer. We also investigated the epigenetic regulation of mtTFA to delineate the role of oxidative stress-mediated inflammation in Lung cancer and COPD. The RT2 Profiler PCR array was used to examine the differential expression pattern of inflammatory genes in CD4+ T helper (Th) cells from COPD, NSCLC, and control subjects. Candidate inflammatory gene loci were selected and the enrichment of tran-scriptional factor and histone modifiers was analysed using ChIP-qPCR. In comparison to control subjects, a set of genes (e.g., BMP2, CCL2, IL5, VEGFA, etc.) are over-expressed whereas another set of genes (e.g., AIMP1, IFNG, LTA, LTB, TNF, etc.) are under-expressed in both COPD and NSCLC patients. The increased percent enrichment of inflammation-associated transcription factors including NF-kB, CREB, HIF1, and MYC at the loci of inflammatory genes was revealed by our chromatin immunoprecipitation (ChIP) data. H3K4me3, H3K9me3, H3K14Ac, HDAC1, 2, 3, 6 all showed dysregulated enrichment at the VEGFA gene locus. One of the epigenetic modifica-tions, histone methylation, was found to be abnormal in the mtTFA complex in COPD and NSCLC patients in comparison to controls. Although there is mounting evidence of several links between these disorders, thera-peutic options remain inadequate. Our findings contribute to the body of knowledge about therapeutic tech-niques that use inflammatory cytokines as a prognostic marker and highlight the need for epigenetic therapy for these debilitating lung diseases. Superscript/Subscript Available
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