Activation of STAT3 is crucial for human B lymphocyte differentiation and inhibition of its phosphorylation in CD40-activated B lymphocytes results in impairment of in vitro generation of immunoglobulin-secreting cells. Conversely, redox homeostasis plays a role in B lymphocyte maturation. Thus, the presence of antioxidants can potentially modulate their outcome. We showed that N-acetylcysteine (NAC), an antioxidant molecule, can inhibit STAT3 phosphorylation, which is paralleled with strong inhibition of immunoglobulins secretion. Western analysis reveals that NAC-treatment of CD40-activated human B lymphocytes, in the presence of IL-2, IL-4 and IL-10, causes a reduced phosphorylation of JAK2 and JAK3, which are important activators of STAT3. Furthermore, this inhibition appears to be dose-dependant. Our results indicate that other antioxidant molecule such as α-tocopherol and trolox do not affect these two kinases phosphorylation. Other kinases or their inhibitors associated to STAT3 phosphorylation do not seem affected by the presence of antioxidant in the media. In conclusion, these observations reveal that STAT3 phosphorylation down regulation in NAC conditions is due to its association with JAK2 and JAK3.
- Copyright © 2013 by The American Association of Immunologists, Inc.