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Protein kinase C-δ is involved in the inflammatory effect of IL-6 in mouse adipose cells

Författare och institution:
Emelie Wallerstedt (Institutionen för medicin, avdelningen för molekylär och klinisk medicin); Ulf Smith (Institutionen för medicin, avdelningen för molekylär och klinisk medicin); Christian X Andersson (Institutionen för medicin, avdelningen för molekylär och klinisk medicin)
Publicerad i:
Diabetologia, 53 ( 5 ) s. 946-954
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Aims/hypothesis The aim of the study was to address the role of protein kinase C-δ (PKCδ) on phosphorylation of signal transducer and activator of transcription 3 (STAT3) and activation of inflammatory genes in response to IL-6 in adipose cells. Methods Differentiated mouse 3T3-L1 adipocytes preincubated with the PKCδ inhibitor rottlerin and mouse embryonic fibroblasts (MEFs) lacking PKCδ were incubated with IL-6 and/or insulin. RNA was extracted and the gene expression was analysed by real-time PCR, while the proteins from total, nuclear and cytoplasmic lysates were analysed by immunoblotting. Results Inhibition of PKCδ by rottlerin significantly reduced both Ser-727 and Tyr-705 phosphorylation of STAT3. Consequently, nuclear translocation of STAT3 and the IL-6-induced gene transcription and protein release of the inflammatory molecule serum amyloid A 3 (SAA3) were reduced. Similarly, the IL-6-regulated gene transcription of Il-6 (also known as Il6) to Hp and the feedback inhibitor of IL-6, Socs3, were also attenuated by rottlerin. Furthermore, PKCδ was found to translocate to the nucleus following IL-6 treatment and this was also reduced by rottlerin. In agreement with the effect of rottlerin, Pkcδ (also known as Prkcd) −/− MEFs also displayed a markedly reduced ability of IL-6 to activate the transcription of Saa3, Hp, Socs3 and Il6 genes compared with wild-type MEFs. These results correlated with a reduced nuclear translocation and phosphorylation of STAT3. Conclusions/interpretation These results show that PKCδ plays a key role in the inflammatory effect of IL-6 in adipose cells and may be a suitable target for novel anti-inflammatory agents.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
3T3-L1, IL-6, Inflammation, Insulin resistance, Obesity, PKC delta, STAT3
Postens nummer:
Posten skapad:
2010-05-05 11:57
Posten ändrad:
2011-10-24 15:12

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