Autoinhibition of IL-15 expression in KC cells is ERK1/2 and PI3K dependent.
Interleukin (IL)-15 is a proinflammatory cytokine and plays a key role in many diseases, including psoriasis. Although its signal transduction pathways in keratinocytes (KC) have been partially elucidated, the effects of IL-15 on expression of IL-15, IL-6 and TNF-alpha in KC are unknown. We have investigated the effects of IL-15 on the expression of the three genes in primary culture of KC by the real-time PCR, Western blot and ELISA. We observed that exogenous IL-15 suppressed the endogenous expression of IL-15, decreased the expression of IL-6 at mRNA and protein levels in KC. The inhibition was blocked by anti-IL-15 monoclonal antibody and by inactive IL-15, I50D mutant IL-15. In contrast, IL-15 increased TNF-alpha transcription in these cells. Mechanistic studies demonstrated that the auto-regulation of IL-15 expression was dependent on activity of ERK1/2 and PI3K. Our studies suggest that there is an auto-inhibitory mechanism controlling cellular IL-15 levels.
Zhang
S-Q
SQ
Institute of Dermatology & Department of Dermatology at the First Hospital, Anhui Medical University, Hefei, Anhui, China.
Luo
X
X
Yang
S
S
Liu
J-L
JL
Yang
C-J
CJ
Yin
X-Y
XY
Huang
H-L
HL
Zhang
X-J
XJ
D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis; D015603:Keratinocytes / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis
D019409:Interleukin-15; D015850:Interleukin-6; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases