CQMUH‐011 mitigates autoimmune hepatitis via inhibiting the function of T lymphocytes

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 dosedependently 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 downregulated 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.

Comprehensive immune cell analysis of human menstrual-blood-derived stem cells therapy to concanavalin A hepatitis

“…CD69 is referred to as a marker for early activated lymphocytes ( 26 ). We noted that ConA administration could give a prominent increase in CD69 + T cells among all CD45 + leukocytes, which were supposed as active T cells ( 36 ). Combining the results of CyTOF and conventional flow cytometry, we found that CD69 + T cells were notably elevated by ConA, and CD69 − T cells were significantly reduced, with total CD4 + T cells showing similar percentage between NC and ConA group, and total CD8 + T cells were significantly reduced by ConA injection.…”

Pien Tze Huang alleviates Concanavalin A-induced autoimmune hepatitis by regulating intestinal microbiota and memory regulatory T cells

“…According to earlier research[ 20 , 21 ], the mice were randomly allocated into 6 groups (10 mice in each group): Control group (control), Concanavalin A (Con A) group (model), Con A + low-dose PTH group (PTH-L), Con A + middle-dose PTH group (PTH-M), Con A + high-dose PTH group (PTH-H), and Con A + DXM group (DXM). Mice in the Con A + PTH-L, Con A + PTH-M, and Con A + PTH-H groups received PTH (117 mg/kg, 234 mg/kg, and 468 mg/kg) every day for 10 d by gavage, respectively, while mice in the normal group and Con A group received the same amount of normal drinking water.…”