Interleukin-4 inhibits platelet-derived growth factor-induced preadipocyte proliferation.
Interleukin-4 (IL-4) activates STAT6 in 3T3-L1 preadipocytes but its functional role is not known. In this report, we first assessed interleukin-4 receptor alpha (IL-4Ralpha) expression during adipogenesis. IL-4Ralpha was highly expressed in proliferating 3T3-L1 preadipocytes. Receptor expression was down-regulated in post-confluent growth arrested preadipocytes. Induction of differentiation led to a transient 36-h increase in expression, but then levels decreased to undetectable amounts 3-8 days after induction of differentiation. Depending on the cell type, IL-4 either increases or decreases cell proliferation. In growth arrested preconfluent 3T3-L1 preadipocytes, IL-4 alone had no effect on preadipocyte proliferation. In contrast, IL-4 inhibited platelet-derived growth factor (PDGF-BB) induced preadipocyte proliferation. PDGF-BB, but not IL-4, induced STAT3 tyrosine and AKT serine phosphorylation. Both PDGF-BB and IL-4 induced STAT6 tyrosine phosphorylation, but the bands showed distinct electrophoretic migration patterns. IL-4 alone and IL-4 added to the differentiation cocktail had no effect on adipocyte formation or PPARgamma expression. Collectively, these studies demonstrate that IL-4 inhibits PDGF-BB-induced preadipocyte proliferation, possibly through STAT6 activation. The pattern of IL-4 receptor expression suggests that the effects of IL-4 are targeted primarily towards preadipocytes.
Hua
Kunjie
K
Department of Nutrition, University of North Carolina at Chapel Hill, NC 27599, USA.
Deng
Jianbei
J
Harp
Joyce B
JB
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D000077214:Becaplermin; D002455:Cell Division / Q000187:drug effects; D015536:Down-Regulation; D015847:Interleukin-4 / Q000494:pharmacology* / Q000502:physiology; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D019948:Receptors, Interleukin-4 / Q000378:metabolism; D050800:STAT6 Transcription Factor; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D018160:Receptors, Cytoplasmic and Nuclear; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D000077214:Becaplermin; D015847:Interleukin-4