RORγt inverse agonist 29

Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.

Imiquimod (IMQ)-induced psoriasiform dermatitis is a widely used murine model in which topical application of IMQ, a Toll-like receptor 7 (TLR7) agonist, triggers innate immune activation in the skin and induces a psoriasis-like inflammatory cascade characterized by epidermal hyperplasia, immune cell infiltration, and cytokine production dominated by the IL-23/IL-17 axis. This inflammatory response is mediated through activation of dendritic cells and downstream induction of IL-23, IL-17A, IL-22, and related pro-inflammatory mediators, recapitulating key features of human plaque psoriasis and enabling mechanistic and therapeutic studies. The model is commonly induced using Aldara (5% IMQ cream) applied topically to murine skin, resulting in rapid onset of erythema, scaling, and thickening that can be quantified as disease severity indices and validated histologically.

The TPA (12-O-tetradecanoylphorbol-13-acetate) and croton oil-induced mouse ear edema model is a well-established acute cutaneous inflammation system used to evaluate topical anti-inflammatory activity by measuring edema formation, neutrophil infiltration, vascular permeability, and cytokine-mediated skin responses in vivo. The inflammatory response is triggered by topical application of phorbol esters (TPA) or croton oil constituents, leading to rapid activation of protein kinase C signaling, leukocyte recruitment, and increased vascular permeability, which can be quantified by ear thickness, weight, dye extravasation, and biochemical markers such as myeloperoxidase (MPO) activity and pro-inflammatory mediators in ear tissue homogenates. This model is widely used for screening anti-inflammatory agents, where reductions in edema and inflammatory biomarkers reflect suppression of acute dermal inflammation and immune cell infiltration. Histological evaluation typically confirms epidermal

Contact hypersensitivity (CHS) dermatitis is a T cell-mediated delayed-type (Type IV) immune reaction in which low-molecular-weight haptens applied to the skin bind host proteins to form complete antigens, triggering sensitization followed by a secondary inflammatory response upon re-exposure (elicitation phase), which is commonly quantified by ear swelling as a readout of skin inflammation in murine models. This model is widely used to study allergic contact dermatitis because it is antigen-specific, reproducible, and reflects key immunological events including dendritic cell activation, T cell priming in draining lymph nodes, and effector T cell-driven tissue inflammation. DNFB- and oxazolone-induced CHS models are standard systems for evaluating both acute and chronic T cell-dependent skin inflammation and for testing immunomodulatory interventions.

The NLRP3 inflammasome is a cytosolic innate immune signaling platform that integrates priming signals and danger-signal activation to promote caspase-1 activation, maturation of IL-1β and IL-18, and gasdermin D-mediated pyroptotic cell death. The core experimental logic is to determine whether inflammatory disease phenotypes are driven by increased NLRP3 expression, ASC-containing inflammasome assembly, caspase-1 cleavage, GSDMD cleavage, and extracellular release of IL-1β/IL-18 rather than by nonspecific cell injury alone. The pathway is strongly linked to inflammation-related disease phenotypes because monosodium urate crystals activate NALP3/NLRP3 inflammasome signaling in gout-like crystal inflammation, cholesterol crystals activate NLRP3 inflammasomes in atherogenesis models, and DSS-induced intestinal inflammation has been reported to involve NLRP3 inflammasome activity. However, experimental colitis studies also show context-dependent protective effects of NLRP3 inflammasome co