| First Author | Zhao J | Year | 2023 |
| Journal | Int Immunopharmacol | Volume | 119 |
| Pages | 110238 | PubMed ID | 37126986 |
| Mgi Jnum | J:335850 | Mgi Id | MGI:7485569 |
| Doi | 10.1016/j.intimp.2023.110238 | Citation | Zhao J, et al. (2023) Toll-like receptor-7 signaling in Kupffer cells exacerbates concanavalin A-induced liver injury in mice. Int Immunopharmacol 119:110238 |
| abstractText | Concanavalin A (ConA) is a plant lectin that can induce immune-mediated liver damage. ConA induced liver damage animal model is a widely accepted model that can mimic clinical acute hepatitis and immune-mediated liver injury in humans. Toll-like receptor-7 (TLR7), a member of the TLR family, plays a key role in pathogen recognition and innate immune activation. The aim of this study was to examine the role of TLR7 in the pathogenesis of ConA-induced liver injury. Acute liver injury was induced by intravenous injection with ConA in WT (wild-type) and TLR7 knockout (KO) mice. Results showed that attenuated liver injury in TLR7-deficient mice, as indicated by increased survival rate, decreased aminotransferase levels, and reduced pathological lesions, was associated with decreased release of pro-inflammatory cytokines in livers. Consistently, significantly decreased proliferation of CD4(+) T cell was detected in ConA-stimulated TLR7-deficient splenocytes, but not in CD3/CD28 stimulated TLR7-deficient CD4(+) T cells. Moreover, TLR7 deficiency in KCs specifically suppressed the expression of TNF-alpha (tumor necrosis factor-alpha). Depletion of KCs abolished the detrimental role of TLR7 in ConA-induced liver injury. Taken together, these results demonstrate that TLR7 can regulate the expression of TNF-alpha in KCs, which is necessary for the full progression of ConA-induced liver injury. |
