Ribosomal Alteration-Derived Signals for Cytokine Induction in Mucosal and Systemic Inflammation: Noncanonical Pathways by Ribosomal Inactivation

Abstract

Ribosomal inactivation damages 28S ribosomal RNA by interfering with its functioning during gene translation, leading to stress responses linked to a variety of inflammatory disease processes. Although the primary effect of ribosomal inactivation in cells is the functional inhibition of global protein synthesis, early responsive gene products including proinflammatory cytokines are exclusively induced by toxic stress in highly dividing tissues such as lymphoid tissue and epithelia. In the present study, ribosomal inactivation-related modulation of cytokine production was reviewed in leukocyte and epithelial pathogenesis models to characterize mechanistic evidence of ribosome-derived cytokine induction and its implications for potent therapeutic targets of mucosal and systemic inflammatory illness, particularly those triggered by organellar dysfunctions.

MicroRNA expression analysis for identification of biomarkers in inflammatory bowel disease subtypes

“…4c). Impairment of ribosome biogenesis induce ER stress leading to proinflammatory cytokine production via NFKB activation with IKK (IKBA kinase ) activity maintained at basal level via IRE1 (inositol-requiring ER-tonucleus signal kinase 1), an ER stress sensor [31]. The significantly downregulated genes in UC, in the present study, included receptor families such as TLR6 via NFKB signaling pathway; downregulation of pro-inflammatory cytokines such as IL6, IL-1A, IFNG through activation of JAK signaling pathway and cytokine-cytokine receptor interaction (Fig.…”

Human Ribosomal RNA-Derived Resident MicroRNAs as the Transmitter of Information upon the Cytoplasmic Cancer Stress

“…28S rRNA has been identified as a novel fusion partner of carcinoma-related genes such as BCL6, BCL11B, IGKV3-20, and COG1 in gastric lymphoma or hematopoietic tumors [ 90 , 91 ]. Mutation or inhibition of specific genes associated with ribosome construction pathway such as DKC1, AROS, and several snoRNAs have been identified to impair normal cell functions and sometimes cause carcinogenesis in various cell types [ 92 – 95 ]. Angiogenin-mediated rRNA transcription has been revealed to be related to squamous cell carcinoma [ 96 ].…”

RNA-Seq on patients with chronic inflammatory response syndrome (CIRS) treated with vasoactive intestinal peptide (VIP) shows a shift in metabolic state and innate immune functions that coincide with healing

“…Over 100 similar acting toxins, called ribosomal inactivating proteins (RIPs) have been identified, mainly in plants, with the most wellknown of the group probably being ricin (for review see (Walsh, Dodd, & Hautbergue, 2013). Ricin and other ribotoxins are known to induce an inflammatory response through selective up regulation of cytokine transcription even while depressing overall protein synthesis (Moon, 2014 With the diminution of ribosomal and mitochondrial functions, and full immune system engagement in response to an inflammagenic, microbial insult, definitive pathology is hard to predict in patient exposures. One of the biggest problems with identifying illness from exposure to WDBs is the scientific certainty that different materials, humidity, temperature, etc., favor the growth of certain microbes over others.…”