Surfactant protein A activation of atypical protein kinase C ζ in IκB-α-dependent anti-inflammatory immune regulation

Christina Moulakakis, Stefanie Adam, Ulrike Seitzer, Andra B. Schromm, Michael Leitges, Cordula Stamme*

*Corresponding author for this work
23 Citations (Scopus)


The pulmonary collectin surfactant protein (SP)-A has a pivotal role in anti-inflammatory modulation of lung immunity. The mechanisms underlying SP-A-mediated inhibition of LPS-induced NF-κB activation in vivo and in vitro are only partially understood. We previously demonstrated that SP-A stabilizes IκB-α, the primary regulator of NF-κB, in alveolar macrophages (AM) both constitutively and in the presence of LPS. In this study, we show that in AM and PBMC from IκB-α knockout/IκB-β knockin mice, SP-A fails to inhibit LPS-induced TNF-α production and p65 nuclear translocation, confirming a critical role for IκB-α in SP-A-mediated LPS inhibition. We identify atypical (a) protein kinase C (PKC) ζ as a pivotal upstream regulator of SP-A-mediated IκB-α/NF- κB pathway modulation deduced from blocking experiments and confirmed by using AM from PKCζ-/- mice. SP-A transiently triggers aPKCThr410/403 phosphorylation, aPKC kinase activity, and translocation in primary rat AM. Coimmunoprecipitation experiments reveal that SP-A induces aPKC/p65 binding under constitutive conditions. Together the data indicate that anti-inflammatory macrophage activation via IκB-α by SP-A critically depends on PKCζ activity, and thus attribute a novel, stimulus-specific signaling function to PKCζ in SP-A-modulated pulmonary immune response.

Original languageEnglish
JournalJournal of Immunology
Issue number7
Pages (from-to)4480-4491
Number of pages12
Publication statusPublished - 01.10.2007


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