In vivo suppression of NF-kappa B and preservation of I kappa B alpha by interleukin-10 and interleukin-13.
IL-10 and IL-13 have powerful antiinflammatory activities in vitro and in vivo. In the IgG immune complex model of lung injury in rats, exogenously administered IL-10 or IL-13 have recently been shown to suppress neutrophil recruitment and ensuing lung injury by greatly depressing pulmonary production of TNF alpha. Transcriptional control of the TNF alpha gene is regulated by the nuclear factor kappa B (NF-kappa B). Activation of NF-kappa B involves the degradation of its cytoplasmic inhibitor I kappa B alpha, allowing the nuclear translocation of NF-kappa B, with ensuing transcriptional activation. In this study, we sought to determine whether the protective effects of IL-10 and IL-13 in IgG immune complex-induced lung injury were mediated by inhibition of NF-kappa B activation. Electrophoretic mobility shift analysis of nuclear extracts from alveolar macrophages and whole lung tissues demonstrated that both IL-10 and IL-13 suppressed nuclear localization of NF-kappa B after in vivo deposition of IgG immune complexes. Western blot analysis indicated that these effects were due to preserved protein expression of I kappa B alpha in both alveolar macrophages and whole lungs. Northern blot analysis of lung mRNA showed that, in the presence of IgG immune complexes, IL-10 and IL-13 augmented I kappa B alpha mRNA expression. These findings suggest that in vivo, IL-10 and IL-13 may operate by suppressing NF-kappa B activation through preservation of I kappa B alpha.
Lentsch
A B
AB
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA.
Shanley
T P
TP
Sarma
V
V
Ward
P A
PA
D000818:Animals; D000936:Antigen-Antibody Complex; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D020672:I-kappa B Proteins; D007074:Immunoglobulin G; D016753:Interleukin-10 / Q000494:pharmacology*; D018793:Interleukin-13 / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D012710:Serum Albumin, Bovine; D014158:Transcription, Genetic / Q000187:drug effects*
D000936:Antigen-Antibody Complex; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D007074:Immunoglobulin G; D018793:Interleukin-13; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016753:Interleukin-10; D000072000:NF-KappaB Inhibitor alpha; D012710:Serum Albumin, Bovine