ALTERED INHIBITORY kappa B ALPHA EXPRESSION IN LPS-STIMULATED ALVEOLAR MACROPHAGES FOLLOWING RESUSCITATED HEMORRHAGIC SHOCK

作者：Papia Guiseppe; Fan Jie; Kapus Andras; Szaszi Katalin; Marshall John C; Tawadros Patrick; Ailenberg Menachem; Rotstein Ori D^*

来源：Shock, 2011, 35(2): 171-177.

DOI：10.1097/SHK.0b013e3181f21d2d

• Hemorrhagic shock
• lung
• inhibitory kappa B
• mRNA stability

Patients resuscitated from hemorrhagic shock are at increased risk for the development of organ dysfunction, particularly acute respiratory distress syndrome. The "two-hit hypothesis" wherein shock/resuscitation (S/R) renders the immune system more responsive to subsequent inflammatory stimuli has been suggested as a major mechanism contributing to organ injury. Previous work has shown that S/R primes alveolar macrophages for increased nuclear factor kappa B (NF-kappa B) translocation in response to LPS, culminating in increased lung cytokine and chemokine production. Inhibitory. B (I. B) is known to be an important regulator of NF-kappa B activity. In this article, we investigated the effect of S/R on regulation of I kappa B alpha expression in response to LPS both in vitro and in vivo. Two discrete effects on I kappa B regulation were observed after S/R, which served to augment NF-kappa B activity. First, antecedent exposure of alveolar macrophages to S/R resulted in increased LPS-induced I kappa B alpha degradation through activation of upstream signaling, an effect that resulted in increased NF-kappa B translocation and cytokine-induced neutrophil chemoattractant gene expression. Second, cells recovered from rodents after S/R had reduced levels of I kappa B mRNA in response to LPS compared with sham/LPS treatment. This effect was primarily due to the ability of S/R to reverse the prolongation of I kappa B mRNA stability observed after LPS-alone treatment. Together, these effects on the important regulatory molecule I kappa B in the macrophage may contribute to the heightened inflammatory response observed after S/R.

• 出版日期2011-2