Interleukin-4 inhibits kappa light chain expression and NF kappa B activation but not I kappa B alpha degradation in 70Z/3 murine pre-B cells.
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.
Clarke
C J
CJ
Kennedy Institute of Rheumatology, Sunley Division, London, Great Britain.
Taylor-Fishwick
D A
DA
Hales
A
A
Chernajovsky
Y
Y
Sugamura
K
K
Feldmann
M
M
Foxwell
B M
BM
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003864:Depression, Chemical; D005786:Gene Expression Regulation / Q000187:drug effects*; D005803:Genes, Immunoglobulin; D017930:Genes, Reporter; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D020672:I-kappa B Proteins; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis* / Q000235:genetics; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D015703:Antigens, CD; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D007375:Interleukin-1; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D011947:Receptors, Antigen, B-Cell; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D015847:Interleukin-4; D004247:DNA; D001616:beta-Galactosidase