INTERLEUKIN-1 MODULATES PHOSPHORYLATION OF PROTEINS IN HUMAN OSTEOBLASTIC CELLS

Interleukin-1 (IL-1) is a potent bone resorbing cytokine with diverse biological effects. We previously reported that IL-1 inhibits PDGF-AA- induced biological activities including PDGF-AA-induced tyrosyl phosph orylation. In the present studies, we first investigated and compared the tyrosyl phosphorylation pattern induced by EGF, IGF-1, PDGF-AA, an d bFGF in human osteoblastic cells. We then examined the effect of IL- 1 on the tyrosyl phosphoproteins induced by each ligand. Immunoblot an alyses show that EGF, IGF-1, and PDGF-AA each elicit a different patte rn of tyrosyl phosphorylated proteins in normal human osteoblastic cel ls, IL-1 beta inhibits PDGF-AA induced autophosphorylation by down-reg ulation of the PDGF-alpha receptor, as demonstrated by immunoprecipita tion experiments. For other ligand-induced tyrosyl phosphoproteins, IL -1 beta reduced the intensity of EGF-induced pp55,000, and IL-1 beta i nduced pp185,000 and pp175,000, These experiments indicate that IL-1 i nhibits phosphorylation of specific proteins induced by growth factors . By using inhibitors of secondary message pathways, we determined tha t the inhibitory effect of IL-1 beta on PDGF-AA receptor binding and r eceptor tyrosyl autophosphorylation was not dependent on protein kinas e A, protein kinase C, or the formation of prostaglandins. These data suggest the existence of an alternative pathway that may participate i n IL-1 beta signaling.