Interleukin-11 receptor is an alternative α-receptor for interleukin-6 and the chimeric cytokine IC7.

The cytokine interleukin 6 (IL-6) signals via the IL-6 α-receptor (IL-6Rα or IL-6R) in complex with the gp130 β-receptor. Cell type restricted expression of the IL-6R limits the action of IL-6 mainly to hepatocytes and some immune cells. Here, we show that IL-6 also binds to the IL-11 α receptor (IL-11Rα or IL-11R) and induces signaling via IL-11R:gp130 complexes, albeit with a lower affinity compared to IL-11.

A refined TTC assay precisely detects cardiac injury and cellular viability in the infarcted mouse heart.

Histological analysis with 2,3,5-triphenyltetrazolium chloride (TTC) staining is the most frequently used tool to detect myocardial ischemia/reperfusion injury. However, its practicality is often challenged by poor image quality in gross histology, leading to an equivocal infarct-boundary delineation and potentially compromised measurement accuracy. Here, we introduce several crucial refinements in staining protocol and sample processing, which enable TTC images to be analyzed with light microscopy.

Synthetic trimeric interleukin-6 receptor complexes with a STAT3 phosphorylation dominated activation profile.

In Interleukin (IL)-6 signalling, IL-6 site I binds to the IL-6 receptor (IL-6R) first, following by IL-6 site II interaction to domain 2/3 of gp130 to form premature trimeric IL-6:IL-6R:gp130 receptor complexes. Formation of the mature hexameric receptor complex is then facilitated by the inter-trimeric interaction of IL-6 site III with domain 1 of the opposing gp130. The two gp130-associated Janus kinases (JAKs) trans-phosphorylate when their spatiotemporal pairing is correct, which causes the activation of STAT, ERK, and AKT pathways in a balanced manner.

Increased Expression of the Neuropeptides PACAP/VIP in the Brain of Mice with CNS Targeted Production of IL-6 Is Mediated in Part by Trans-Signalling.

Inflammation with expression of interleukin 6 (IL-6) in the central nervous system (CNS) occurs in several neurodegenerative/neuroinflammatory conditions and may cause neurochemical changes to endogenous neuroprotective systems. Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are two neuropeptides with well-established protective and anti-inflammatory properties. Yet, whether PACAP and VIP levels are altered in mice with CNS-restricted, astrocyte-targeted production of IL-6 (GFAP-IL6) remains unknown.

Intratumoral Delivery of Genetically Engineered Anti-IL-6 Trans-signaling Therapeutics.

Interleukin-6 (IL-6) is a highly pro-inflammatory cytokine involved in the etiopathology of several inflammatory diseases and cancer. As so, the inhibition of IL-6 signaling pathways has emerged as an attractive therapeutic avenue for the treatment of several chronic diseases. Since IL-6 trans-signaling was described as the pathological branch of IL-6, selective inhibitors were developed.