CQMUH-011 mitigates autoimmune hepatitis via inhibiting the function of T lymphocytes.
Drug Dev Res
; 82(8): 1111-1123, 2021 12.
Article
in En
| MEDLINE
| ID: mdl-33733518
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sulfonamides
/
Adamantane
/
T-Lymphocytes
/
Hepatitis, Autoimmune
/
Anti-Inflammatory Agents
Limits:
Animals
Language:
En
Journal:
Drug Dev Res
Year:
2021
Type:
Article
Affiliation country:
China