MaxiK blockade selectively inhibits the lipopolysaccharide-induced IκB-α/NF-κB signaling pathway in macrophages

Martin Papavlassopoulos, Cordula Stamme, Lutz Thon, Dieter Adam, Doris Hillemann, Ulrich Seydel, Andra B. Schromm*

*Corresponding author for this work
43 Citations (Scopus)


Macrophages have a pivotal function in innate immunity against bacterial infections. They are present in all body compartments and able to detect invading microorganisms with high sensitivity. LPS (endotoxin) of Gram-negative bacteria is among the most potent stimuli for macrophages and initiates a wide panel of cellular activation responses. The release of mediators such as TNF-α and ILs is essential for the initiation of a proinflammatory antibacterial response. Here, we show that blockade of the large-conductance Ca2+-activated potassium channel MaxiK (BK) inhibited cytokine production from LPS-stimnlated macrophages at the transcriptional level. This inhibitory effect of channel blockade was specific to stimulation with LPS and affected neither stimulation of macrophages with the cytokine TNF-α nor LPS-induced activation of cells that do not express MaxiK. Investigation of the npsiream intracellular signaling pathways induced by LPS revealed that the blockade of MaxiK selectively inhibited signaling pathways leading to the activation of the transcription factor NF-κB and the MAPK p38, whereas activation of ERK was unaffected. We present data supporting that proximal regulation of the inhibitory factor IκB-α is critically involved in the observed inhibition of NF-κB translocation. Using alveolar macrophages from rats, we could show that the necessity of MaxiK function in activation of NF-κB and subsequent cytokine production is not restricted to in vitro-generated monocyte-derived macrophages but also can be observed in primary cells. Thus, MaxiK appears to be a central molecule in the NF-κB- dependent inflammatory response of macrophages to bacterial LPS.

Original languageEnglish
JournalJournal of Immunology
Issue number6
Pages (from-to)4086-4093
Number of pages8
Publication statusPublished - 15.09.2006


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