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Gene expression profiling identifies STAT3 as a novel pathway for immunomodulation by cholera toxin adjuvant.

Artikel i vetenskaplig tidskrift
Författare A Sjöblom-Hallén
Annika Nerstedt
Karin Schön
Lena Ekman
Peter Bergqvist
B Löwenadler
Nils Y Lycke
Publicerad i Mucosal immunology
Volym 3
Nummer/häfte 4
Sidor 374-386
ISSN 1935-3456
Publiceringsår 2010
Publicerad vid Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi
Institutionen för medicin, avdelningen för molekylär och klinisk medicin
Sidor 374-386
Språk en
Länkar dx.doi.org/10.1038/mi.2010.16
Ämneskategorier Mikrobiologi inom det medicinska området

Sammanfattning

Earlier studies have reported on both proinflammatory and anti-inflammatory activities of cholera toxin (CT). As CT is a powerful adjuvant, we were interested in identifying genes with a possible involvement in these functions. A global gene expression analysis in mouse B cells showed that CT regulated <100 annotated genes, which encoded transcription factors, G proteins, cell-cycle regulators, and immunoregulating molecules. Interestingly, CT regulated the expression of the signal transducer and activator of transcription (STAT)3 gene and influenced the level and activation of both isoforms STAT3alpha and STAT3beta, in vitro in a B-cell line and in Peyer's patch (PP) B cells and in vivo in freshly isolated splenic B cells from CT-treated mice. This effect was cAMP dependent and was not seen with CTB. B cells pre-exposed to CT were significantly more susceptible to the activation of STAT3 by interleukin (IL)-6 and IL-10. This exerted a stronger inhibitory effect of IL-10 on lipopolysaccharide (LPS)-stimulated B-cell proliferation and cytokine production (IL-6). Moreover, IgG1 and IgA production induced by LPS and IL-10 were enhanced by the addition of CT to cultures of PP or splenic B cells. This is the first study to provide a molecular mechanism that can reconcile previous findings of proinflammatory and anti-inflammatory effects by CT adjuvant.Mucosal Immunology advance online publication 7 April 2010. doi:10.1038/mi.2010.16.

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