Journal: Frontiers in Immunology

Article Title: Cytokines and related signaling pathways in traumatic brain injury

doi: 10.3389/fimmu.2026.1738589

Figure Lengend Snippet: Interleukins play a role in the regulation of neuroinflammation following TBI. Exogenous IL-2 has been shown to enhance neuroprotection by increasing the population of regulatory T cells (Tregs) and suppressing microglial activity. Additionally, IL-2 reduces levels of pro-inflammatory cytokines IL-1β and TNF-α, while promoting the release of the anti-inflammatory factor TGF-β1. Elevated levels of IL-10 during the acute phase of TBI inhibit astrocyte activation through the suppression of NOX production via the activation of the STAT3 signaling pathway. Furthermore, IL-10 inhibits macrophage autophagy by blocking the AMPK/mTOR signaling pathway. Regarding neurotoxicity, increased levels of IL-1 have been shown to compromise the integrity of the blood-brain barrier, leading to the infiltration of peripheral immune cells and the release of inflammatory mediators that activate microglia. In contrast, IL-12 has been found to promote the differentiation of cytotoxic NK cells and the secretion of IFN-γ, thereby intensifying the inflammatory response. Additionally, elevated levels of IL-18 have been implicated in the perpetuation of chronic neuroinflammation, resulting in heightened neuronal apoptosis and dysfunction.

Article Snippet: Pro-inflammatory cascades predominate acutely: injured neurons release DAMPs and HMGB1, which engage TLR4 on microglia, triggering MyD88-dependent NF-κB nuclear translocation to upregulate NLRP3 and GMF expression, thereby accelerating IL-1β and IL-18 release; Galectin-3 amplifies this response via TLR4 binding, while ligand-induced MAPK (p38/JNK/ERK) phosphorylation promotes microglial activation, oxidative stress, and blood-brain barrier disruption—collectively driving early apoptosis, edema, and gliosis.

Techniques: Activity Assay, Activation Assay, Blocking Assay

Journal: Frontiers in Immunology

Article Title: Cytokines and related signaling pathways in traumatic brain injury

doi: 10.3389/fimmu.2026.1738589

Figure Lengend Snippet: An overview of cytokine factors related signaling pathways that are involved in TBI. I. Injured neurons release damage-associated molecular patterns (DAMPs) and HMGB1, which bind to TLR4. This activates microglia to produce more inflammatory factors and Galectin-3. At the same time, it initiates a cascade reaction with MyD88, promoting the entry of NF-κB into the nucleus to bind to the promoter and up-regulate the expression of NLPR3 and GMF. This accelerates the release of IL-1β and IL-18. Galectin-3 can also initiate an inflammatory response by binding to the TLR4 receptor. II. The binding of ligands (growth factors and cytokines) to specific receptors triggers a cascade reaction of MAPKs. These are activated by phosphorylation and ultimately induce microglia activation, oxidative stress, and blood-brain barrier damage. III. TGFβ1 binds to the receptor and initiates Smads protein phosphorylation. This inhibits microglia activation and protects the nerves, preventing myelin shedding. IV. After TBI, epidermal growth factor and insulin growth factor bind to tyrosine kinase receptors, initiating a cascade reaction that activates Akt. Akt participates in apoptosis by regulating the phosphorylation of the pro-apoptotic mediator GSK-3β.

Article Snippet: Pro-inflammatory cascades predominate acutely: injured neurons release DAMPs and HMGB1, which engage TLR4 on microglia, triggering MyD88-dependent NF-κB nuclear translocation to upregulate NLRP3 and GMF expression, thereby accelerating IL-1β and IL-18 release; Galectin-3 amplifies this response via TLR4 binding, while ligand-induced MAPK (p38/JNK/ERK) phosphorylation promotes microglial activation, oxidative stress, and blood-brain barrier disruption—collectively driving early apoptosis, edema, and gliosis.

Techniques: Protein-Protein interactions, Expressing, Binding Assay, Phospho-proteomics, Activation Assay

Journal: Cellular and Molecular Gastroenterology and Hepatology

Article Title: Loss of NKCC1 Activates the NLRP3 Inflammasome in Intestinal Epithelia

doi: 10.1016/j.jcmgh.2025.101681

Figure Lengend Snippet: Deletion of NKCC1 increases NLRP3 inflammasome activation. ( A ) Caco-2 cells and NKCC1-KO clones were primed overnight with LPS prior to stimulation with ATP or HBSS as control for 20 minutes. IL-1β (pro and cleaved form) level in the supernatant and in cell lysate was assessed by western blotting. ( B–D ) Graph showing densitometric analysis of IL-1β cleaved fragments in the supernatant of cells shown in ( A ). Immunoreactive bands in the supernatant were normalized to protein concentrations in the supernatant and immunoreactive bands in cell lysates were normalized to β-actin. ( E ) IL-1β secretion in Caco-2 and NKCC1-KO clones was measured by ELISA. ( F ) Western blot showing IL-18 in supernatant and lysates of Caco-2 cells with and without NKCC1 treated or not with ATP. ( G–H ) Quantitation of data shown in ( F ). ( I ) IL-18 secretion measured by ELISA. ( J ) HT29 cells and NKCC1-edited (KO) clone C4 were primed overnight with LPS prior to incubation with ouabain, ATP, or vehicle as control for 15 to 60 minutes. IL-1β (pro and cleaved form) level in the supernatant and in cell lysates were assessed by immunoblotting. ∗ P < .05, ∗∗ P < .01, ∗∗∗ P < .001 2-way ANOVA, Tukey’s multiple comparison test. All error bars = mean ± SEM.

Article Snippet: IL-1β and IL-18 release into cell culture supernatants after the various treatment was determined by ELISA using the Human IL-1β/IL-1F2 and IL-18/IL-1F4 Quantikine ELISA kits (R&D Systems), according to the manufacturer’s instructions.

Techniques: Activation Assay, Clone Assay, Control, Western Blot, Enzyme-linked Immunosorbent Assay, Quantitation Assay, Incubation, Comparison

Journal: Cellular and Molecular Gastroenterology and Hepatology

Article Title: Loss of NKCC1 Activates the NLRP3 Inflammasome in Intestinal Epithelia

doi: 10.1016/j.jcmgh.2025.101681

Figure Lengend Snippet: IL-1β release and caspase-1 activation in the fibroblast of UDP-2780 patient. ( A ) UDP-2780 and control fibroblasts were stimulated with ATP for 20 minutes or left untreated (controls). IL-1β (pro and cleaved form) level in the supernatant and in cell lysate was assessed by Western blotting. ( B–C ) Graph shows densitometric analysis of blots shown in ( A ). ( D–E ) IL-18 in supernatant and cell lysate. Caspase-1 cleavage ( F–H ) and gasdermin cleavage ( I–K ) are also increased in human NKCC1-deficient fibroblasts. ∗∗∗ P < .001 2-way ANOVA, Tukey’s multiple comparison test. All error bars = mean ± SEM.

Article Snippet: IL-1β and IL-18 release into cell culture supernatants after the various treatment was determined by ELISA using the Human IL-1β/IL-1F2 and IL-18/IL-1F4 Quantikine ELISA kits (R&D Systems), according to the manufacturer’s instructions.

Techniques: Activation Assay, Control, Western Blot, Comparison