IADR Abstract Archives

Valsartan suppresses LPS-induced inflammation in macrophages independently of AT1 receptor

Objectives: Angiotensin II receptor blockers (ARBs), used for treating patients with hypertension, have insulin-sensitizing effects. However, underlying molecular pathways are not fully understood yet. We have shown that a kind of ARB, valsartan improves LPS-induced insulin signaling impairment in adipocytes co-cultured with macrophages. The aim of this study is to elucidate the molecular mechanism underlying the insulin-sensitizing effect of the ARB, valsartan as demonstrated in some clinical studies.

Methods: To examine whether or not valsartan exerts its effect via the targets of ARB, angiotensin II receptor AT1, we carried out two separate experiments, one using macrophages from AT1a knockout mice and the other THP-1 cells treated with AT1 siRNA. We also investigated whether or not the effect of valsartan was inhibited by a peroxisome proliferator-activated receptor (PPAR)γ antagonist, GW9662. The cells were treated with the indicated concentrations of Escherichia coli LPS in the presence or absence of valsartan for the indicated times. The mRNA levels of inflammatory cytokines in macrophages treated with LPS and valsartan were measured by real-time PCR.

Results: In macrophages from AT1a knockout mice, valsartan markedly suppressed LPS-induced increases in cytokine mRNA levels, essentially the same effect that this drug had in control mice. This suppressive effect of valsartan was also observed in THP-1 cells treated with AT1 siRNA or GW9662.

Conclusion: Valsartan suppresses the inflammatory response of macrophages, though not via PPAR γ or AT1a receptor.


Japanese Division Meeting
2011 Japanese Division Meeting (Hiroshima, Japan)
Hiroshima, Japan
2011

Scientific Groups
  • Iwashita, Misaki  ( Hiroshima University, Hiroshima, N/A, Japan )
  • Asano, Tomoichiro  ( Hiroshima University, Hiroshima, N/A, Japan )
  • Nishimura, Fusanori  ( Hiroshima University, Hiroshima, N/A, Japan )
    • Microbiology/Immunology