Premium
Hydrogen Peroxide Increases Interleukin‐12 p40/p70 Molecular Ratio and Induces Th2‐Predominant Responses in Mice
Author(s) -
Obata F.,
Hoshino A.,
Toyama A.
Publication year - 2006
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2005.01718.x
Subject(s) - ovalbumin , immune system , cytokine , lipopolysaccharide , antibody , spleen , hydrogen peroxide , chemistry , microbiology and biotechnology , interleukin 12 , in vitro , messenger rna , biology , immunology , cytotoxic t cell , biochemistry , gene
To investigate the influence of oxidative stress on the immune response, mice were injected with H 2 O 2 , and peritoneal macrophages were isolated and stimulated in vitro with lipopolysaccharide (LPS). H 2 O 2 significantly augmented both interleukin (IL)‐12p40 and IL‐12p70 production and increased the p40/p70 molecular ratio. This was confirmed by mRNA analysis, which showed that H 2 O 2 increased LPS‐induced mRNA expression of both IL‐12p40 and IL‐12p35 subunits with an increased p40/p35 ratio. Analysis of anti‐ovalbumin (OVA) antibodies revealed that H 2 O 2 injection significantly increased the production of type 2 helper T cell (Th2)‐associated antibody classes [immunoglobulin (Ig)E and IgG1] but not a Th1‐associated antibody class (IgG2a). To confirm the Th2‐predominant immune response, we analyzed the profile of cytokine production by spleen T cells of OVA‐immunized and H 2 O 2 ‐injected mice. H 2 O 2 significantly increased the production of IL‐4 but not that of interferon‐γ. Together, these results suggest that H 2 O 2 ‐induced overproduction of IL‐12p40 promotes the Th2‐predominant response through increased production of IL‐12p40‐homodimers, which could serve as an antagonist of the Th1‐inducing cytokine IL‐12p70.