| First Author | Wallerstedt E | Year | 2010 |
| Journal | Diabetologia | Volume | 53 |
| Issue | 5 | Pages | 946-54 |
| PubMed ID | 20151299 | Mgi Jnum | J:161764 |
| Mgi Id | MGI:4461191 | Doi | 10.1007/s00125-010-1668-1 |
| Citation | Wallerstedt E, et al. (2010) Protein kinase C-delta is involved in the inflammatory effect of IL-6 in mouse adipose cells. Diabetologia 53(5):946-54 |
| abstractText | AIMS/HYPOTHESIS: The aim of the study was to address the role of protein kinase C-delta (PKCdelta) 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 PKCdelta inhibitor rottlerin and mouse embryonic fibroblasts (MEFs) lacking PKCdelta 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 PKCdelta 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, PKCdelta 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, Pkcdelta (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 PKCdelta 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. |
