Interleukin‑6 signalling as a valuable cornerstone for molecular medicine (Review).
Interleukin‐6, SARS‐CoV‐2, IL‑6 nanoparticle assembly, classic signalling, cognitive IL‑6 model, inflammatory IL‑6 model, let‑7g‑7c, miR‑142‑3p, trans‑signalling
The biological abilities of interleukin‑6 (IL‑6) have been under investigation for nearly 40 years. IL‑6 works through an interaction with the complex peptide IL‑6 receptor (IL‑6R). IL‑6 is built with four α‑chain nanostructures, while two different chains, IL‑6Rα (gp80) and gp130/IL6β (gp130), are included in IL‑6R. The three‑dimensional shapes of the six chains composing the IL‑6/IL‑6R complex are the basis for the nanomolecular roles of IL‑6 signalling. Genes, pseudogenes and competitive endogenous RNAs of IL‑6 have been identified. In the present review, the roles played by miRNA in the post‑transcriptional regulation of IL‑6 expression are evaluated. mRNAs are absorbed via the 'sponge' effect to dynamically balance mRNA levels and this has been assessed with regard to IL‑6 transcription efficiency. According to current knowledge on molecular and nanomolecular structures involved in active IL‑6 signalling, two different IL‑6 models have been proposed. IL‑6 mainly has functions in inflammatory processes, as well as in cognitive activities. Furthermore, the abnormal production of IL‑6 has been found in patients with severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2; also known as COVID‑19). In the present review, both inflammatory and cognitive IL‑6 models were analysed by evaluating the cytological and histological locations of IL‑6 signalling. The goal of this review was to illustrate the roles of the classic and trans‑signalling IL‑6 pathways in endocrine glands such as the thyroid and in the central nervous system. Specifically, autoimmune thyroid diseases, disorders of cognitive processes and SARS‑CoV‑2 virus infection have been examined to determine the contribution of IL‑6 to these disease states.
Maria Trovato, Salvatore Sciacchitano, Alessio Facciolà, Andrea Valenti, Giuseppa Visalli, Angela Di Pietro
International journal of molecular medicine