PKCepsilon induces interleukin-6 expression through the MAPK pathway in 3T3-L1 adipocytes.
Recent reports have suggested that PKCepsilon contributes to systemic insulin resistance, and is involved in the pathogenesis of type 2 diabetes, however, the exact mechanism is still unknown. To elucidate the possible involvement of PKCepsilon in the pathogenesis of type 2 diabetes, we examined the role of PKCepsilon in differentiated adipocytes using mouse 3T3-L1 adipocytes. We found that the over-expression of PKCepsilon resulted in the increase of IL-6 expression in differentiated adipocytes. This PKCepsilon-induced IL-6 expression could be completely inhibited by U0126, an inhibitor of mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase. We also demonstrated that PKCepsilon increased the transcriptional activity of Est-like transcription factor (Elk-1) as well as the DNA-binding activity of activator protein-1 (AP-1) in differentiated 3T3-L1 adipocytes. These results suggest that PKCepsilon is able to increase IL-6 expression via the ERK-AP-1 pathway in differentiated adipocytes, and that PKCepsilon is involved in systemic insulin resistance by regulating plasma IL-6 concentrations.
Ohashi
Kana
K
SNP Research Center, The Institute of Physical and Chemical Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Kanazawa
Akio
A
Tsukada
Shuichi
S
Maeda
Shiro
S
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D007333:Insulin Resistance / Q000502:physiology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology*; D051744:Protein Kinase C-epsilon; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D015850:Interleukin-6; D014157:Transcription Factors; C497256:Prkce protein, mouse; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon; D020928:Mitogen-Activated Protein Kinases