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  • Title: NF-kappaB activation during IgG immune complex-induced lung injury: requirements for TNF-alpha and IL-1beta but not complement.
    Author: Lentsch AB, Czermak BJ, Bless NM, Ward PA.
    Journal: Am J Pathol; 1998 May; 152(5):1327-36. PubMed ID: 9588901.
    Abstract:
    The development of acute lung inflammatory injury induced by alveolar deposition of IgG immune complexes in rats requires increased production of the proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) as well as the complement activation product, C5a. Transcription of TNF-alpha and IL-1beta genes are known to be regulated by the nuclear factor-kappa B (NF-kappaB). During IgG immune complex-induced lung inflammation, NF-kappaB has been shown to be activated in both alveolar macrophages and whole lung tissues. In the current studies we sought to determine whether TNF-alpha, IL-1beta, the complement system and oxidants contribute to the activation of NF-kappaB in the lung. Electrophoretic mobility shift analysis of nuclear extracts from whole lung tissues demonstrated that NF-kappaB activation induced by the presence of IgG immune complexes occurred independently of the complement system and neutrophils. Intrapulmonary instillation of TNF-alpha or IL-1beta into normal lung induced NF-kappaB, whereas C5a was incapable of causing NF-kappaB activation. In alveolar macrophages stimulated in vitro with IgG immune complexes, NF-kappaB activation was greatly attenuated in the presence of antibodies to TNF-alpha or IL-1beta. Similarly, in vivo blockade of TNF-alpha or IL-1beta suppressed lung NF-kappaB activation during IgG immune complex-induced lung injury. N-acetylcysteine, but not catalase, suppressed activation of lung NF-kappaB. These data suggest that TNF-alpha and IL-1beta function in an autocrine or paracrine manner to amplify the lung inflammatory response through activation of NF-kappaB. Oxidants not derived from neutrophils also appear to play a role in this process, whereas complement activation products are not involved in this phenomenon.
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