Induction of IL-6 gene expression in Kaposi's sarcoma cells.
IL-6 is a multifunctional cytokine that functions as an autocrine growth factor for AIDS-derived Kaposi's sarcoma (KS) cells. We report that IL-6 is highly inducible at both the mRNA and protein levels in cultured KS cells by multiple agents, yet the effect of the IL-6 on the proliferation of KS cells is dependent on the agent responsible for its induction. Both IL-1 beta and the synthetic dsRNA, poly (I:C), induced high levels of IL-6 mRNA and protein expression, whereas LPS and TNF-alpha led to only modest increases in IL-6 protein and mRNA. When KS cells were incubated with poly (I:C) in combination with either IL-1 beta or TNF-alpha, there was a synergistic increase in the level of IL-6 production, whereas LPS and TNF-alpha in combination led to only an additive increase in the level of IL-6 production. Exogenous IL-6 was shown to induce proliferation in KS cells, yet there was a dramatic inhibition of proliferation in response to poly (I:C), despite the high levels of IL-6 produced. This inhibition of proliferation by poly (I:C) was unlikely as a result of expression of class I IFN in response to the poly (I:C) because high concentrations of exogenous IFN-alpha had no demonstrable effect on [3H]TdR incorporation under conditions in which poly (I:C) caused a 90% decrease in [3H]TdR incorporation. Pretreatment of KS cells with poly (I:C) for 24 h followed by removal of the poly (I:C) led to high levels of IL-6 secreted into medium that induced proliferation in KS cells. These data suggest that in vivo, multiple agents that occur in response to infection and systemic disease could induce IL-6 production by KS cells, yet the ability of the IL-6 to influence proliferation of KS cells is dependent on the context in which the IL-6 is induced.
Yang
J
J
Winship Cancer Center, Atlanta, GA 30322.
Hagan
M K
MK
Offermann
M K
MK
D002455:Cell Division; D004727:Endothelium / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015658:HIV Infections / Q000150:complications; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D012514:Sarcoma, Kaposi / Q000235:genetics* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D011070:Poly I-C