Oxidative microenvironment exerts an opposite regulatory effect on cytokine production by Th1 and Th2 cells.
Oxidative stress occurs in allergic disorders and immunologic inflammatory responses and reactive oxygen metabolites have an additional role of cell-signaling mediators, influencing many biological processes. Using in vitro derived Th1 and Th2 clones or T cells derived from autoimmune thyroiditis we study the ability of Th1 or Th2 cells to expand and produce cytokine in an oxidative environment. We found that low-doses of H2O2 reduce the INF-gamma production of activated Th1 clones and potentiate the IL-4 secretion of activated Th2 clones. These effects were not due to altered cell proliferation and are not transient, since the modified secretion profile was still retained after 1 week from H2O2 stimulation by both Th1 and Th2 cells. H2O2 influence the profile of cytokine secretion in both Th1 and Th2. These effects are long lasting and are the result of an action of H2O2 on T cell. In conclusion we demonstrate that oxidative stress plays an important role in the pathogenesis of allergic respiratory diseases and can up-regulate Th2-driven inflammation, thus contributing to increase disease severity, bronchial hyper-responsiveness and airway remodeling.
Frossi
Barbara
B
Department of Biomedical Science and Technologies, P.le Kolbe 4, University of Udine, Italy. bfrossi@mail.dstb.uniud.it
De Carli
Marco
M
Piemonte
Marco
M
Pucillo
Carlo
C
D000941:Antigens / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects; D010641:Phenotype; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*; D013961:Thyroid Gland / Q000187:drug effects / Q000276:immunology; D013997:Time Factors
D000941:Antigens; D016207:Cytokines; D007371:Interferon-gamma; D006861:Hydrogen Peroxide