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- Title
CQMUH‐011 mitigates autoimmune hepatitis via inhibiting the function of T lymphocytes.
- Authors
Ling, Qiao; Hu, Xiangnan; Jiang, Rong; Liu, Hailin; Qiu, Hongmei; Jiang, Xuejun; Zubreri, Abdallah; Zhu, Hongda; Wan, Jingyuan; Liu, Yingju
- Abstract
CQMUH‐011 is a modified adamantane sulfonamide compound, that inhibits macrophage proliferation and possesses anti‐inflammatory properties. Here, fresh mouse splenocytes were obtained and stimulated with concanavalin A (ConA, 5 μg/ml) in vitro; and experimental autoimmune hepatitis (AIH) was induced by ConA (20 mg/kg, iv) in vivo, to clarify the protective effects of CQMUH‐011 against AIH and its possible mechanisms. Our results demonstrated that CQMUH‐011 pretreatment can dose‐dependently inhibit the proliferation of splenocytes in vitro. In vivo, CQMUH‐011 administration reduced the hepatic histopathological score and the infiltration of lymphocytes in the liver parenchyma; additionally, it downregulated the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and pro‐inflammatory cytokines interferon (IFN)‐γ, tumor necrosis factor (TNF)‐α, and interleukin (IL)‐6 in serum, as well as those of methane dicarboxylic aldehyde and myeloperoxidase in the liver tissues. It also down‐regulated the expression of p‐NF‐κB and related proteins in the liver tissues. Furthermore, CQMUH‐011 could maintain the balance of CD3+CD4+/CD3+CD8+ and decrease the percentages of CD8+CD69+ and CD4+CD25+/‐CD69+ T‐cells in the splenocytes of ConA‐challenged mice. Moreover, we found thatCD4+CD25+/−CD69+ T‐cells were significantly correlated with ALT levels, especially CD4+CD25−CD69+ T‐cells. In conclusion, CQMUH‐011 exerts potential protective effects against ConA‐induced hepatitis, which may be partially attributed to its inhibition of T cells, especially the suppression of the proliferation of CD4+CD25−CD69+ and CD8+CD69+ subsets in the spleen. CQMUH‐011 also reduced the early apoptosis of lymphocytes in the thymus.
- Subjects
CHRONIC active hepatitis; T cells; TUMOR necrosis factors; LIVER proteins; CONCANAVALIN A; ALANINE aminotransferase
- Publication
Drug Development Research, 2021, Vol 82, Issue 8, p1111
- ISSN
0272-4391
- Publication type
Article
- DOI
10.1002/ddr.21813