Interleukin‐4 inhibits χ light chain expression and NFχB activation but not IχBα degradation in 70Z/3 murine pre‐B cells

Abstract

The murine pre-B cell line 70Z/3 responds to lipopolysaccharide by up-regulating the surface expression of kappa (kappa) light chain through activation of the transcription factor NF kappa B. Interleukin-4 (IL-4), a T cell cytokine, is a known inhibitor of some LPS-mediated events. We investigated whether IL-4 could inhibit the up-regulation of kappa light chain and activation of NF kappa B by LPS in 70Z/3. IL-4 partially inhibited both the LPS-induced expression of kappa light chain and also the activation of NF kappa B as judged by an NF kappa B reporter gene assay. Additionally, electrophoretic mobility shift assays confirmed this effect on LPS-induced NF kappa B DNA binding activity in the nucleus. Surprisingly, proteolytic degradation of I kappa B alpha (MAD3), a prerequisite for NF kappa B activation, was unaffected by IL-4, implying that this cytokine inhibits some subsequent undefined event in the activation of NF kappa B. IL-4 was also found partially to inhibit NF kappa B activity induced by tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta). These results indicate that there may be a common mechanism for the well-documented anti-inflammatory effects of IL-4 and that this mechanism involves the transcription factor NF kappa B.

Heterogeneous requirement of IκB kinase 2 for inflammatory cytokine and matrix metalloproteinase production in rheumatoid arthritis: Implications for therapy

“…The antibody recognizing Ser 32-36 phosphorylated I B␣ was purchased from Cell Signaling Technology (Hitchin, UK). Nuclear extracts (10 g) were examined for NF-B DNA-binding activity using EMSA, as previously described (47).…”

Activation of NF-κB by the intracellular expression of NF-κB-inducing kinase acts as a powerful vaccine adjuvant

“…Cytosolic and nuclear extracts of DCs were prepared as described (43). Cytosolic proteins were analyzed by Western blotting for I B␣, and nuclear extracts (10 g) for NF-B DNA-binding activity were analyzed by EMSA.…”

Blimp-1 Induced by IL-4 Plays a Critical Role in Suppressing IL-2 Production in Activated CD4 T Cells

“…While investigating the phenotypes of the resulting Th2 type cells, we observed that the Th2 effector CD4 T cells were poor IL-2 producers while acquiring the capacity to produce Th2 effector cytokines such as IL-4, IL-10, and IL-13 upon restimulation (supplemental materials). 4 In contrast, CD4 T cells stimulated without basophils or with IL-4-deficient basophils failed to produce Th2 cytokines but preserved IL-2-producing capacity (supplemental material). Given that IL-4, directly involved in Th2 differentiation, has long been known to suppress IL-2 production in activated T cells (9), these results prompted us to propose the hypothesis that IL-4 induces a factor that negatively control IL-2 production in activated CD4 T cells.…”

“…In macrophages or LPS-stimulated monocytes, IL-4 was shown to inhibit the production of TNF-␣, IL-1␤, and IL-12 (1,2), and to suppress expression of Fc␥R and of metalloproteinase (2,3). IL-4 was also demonstrated to inhibit expression of L chain and NF-B activation in murine pre-B cells (4). In mast cells, IL-4 inhibited TNF-␣ production and FcRI expression (5,6).…”