13 Additionally, natural agonists of TRPM8 have been utilized for the treatment of various inflammatory conditions and viral infections. 19 Moreover, TRPM8 has been reported to inhibit the release of neuropeptide from sensory neurons and exert effects on CD11c + dendritic cells to alleviate experimental colitis. ![]() 15 Activation of TRPM8 induces an increase in interleukin-10 release, a reduction in tumor necrosis factor release by macrophages 16, 17 and is beneficial for T-cell activation 18 and differentiation into effector cells. 7, 8 Recent studies have indicated that TRPM8 can modulate the immune response, 9 including in the skin, 10 lung, 11 and intestine, 12 – 14 as well as affect Coxsackievirus B replication. The Corneal TRPM8 channel is implicated in cold sensation, 3, 4 pain sensation, 5 corneal epithelial wound healing, 6 and the mediation of tear secretion. These findings suggest that targeting TRPM8 could be valuable for therapeutic interventions against HSV-1 infections. TRPM8 promoted host resistance to HSV-1 infection by suppressing the accumulation of Ly6G + CD11b + cells and virus replication. Subconjunctival administration of menthol effectively alleviated infection-induced symptoms and Ly6G + CD11b + cell infiltration in herpes simplex virus type 1 (HSV-1)–treated mice. Additionally, TRPM8-deficient mice displayed increased levels of corneal viral titers after infection, along with decreased expression of interferon-stimulated genes (ISGs). Infection in TRPM8-deficient mice resulted in significant lymphocyte infiltration, primarily consisting of Ly6G + CD11b + cells. The anti-inflammatory effect of TRPM8 agonist menthol was documented via subconjunctival administration.Ĭompared to their wild-type counterparts, TRPM8-deficient mice exhibited exacerbated infection symptoms and thicker corneas in HSK models. RNA-sequencing was conducted to elucidate the transcriptome of corneal epithelium in response to TRPM8 knockout after infection. Viral titers were determined by plaque assay and absolute quantitative method. The infected corneas were graded and harvested to evaluate the mRNA levels of inflammatory factors through quantitative real-time polymerase chain reaction (RT-PCR), as well as the infiltration of inflammatory cells through immunofluorescence staining and flow cytometry. HSK models were established using TRPM8 knockout (TRPM8 −/−) mice and their wild-type (WT) littermates. To reveal the role of transient receptor potential cation subfamily M member 8 (TRPM8) channels in herpes simplex keratitis (HSK).
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