INTERLEUKIN 8 (IL-8) STIMULATES AND MAP KINASE KINASE (MEK1) INHIBITOR POTENTIATES PROTEIN TYROSINE KINASE (PTK) ACTIVITY IN NEWBORN LAMB MIDDLE CEREBRAL ARTERIES (MCA) • 436

PTK plays an important role in intracellular signal transduction pathways leading to a complex expression of cellular response(s). IL-8, an α(C-X-C) subfamily of chemokine, is reported to be a circulating factor implicated in reperfusion injury and pediatric hypothermic cardiopulmonary bypass procedure. However, its post-receptor signalling pathway(s) in cerebral circulation is poorly understood. We have preliminarily studied regulatory aspects of IL-8 on PTK of isolated MCA preparations of newborn lambs. PTK activities [PTK] were measured on soluble fraction [sPTK] and particulate fraction [pPTK] (100,000xgx1h) using a synthetic peptide (MW = 1,520) substrate RR-SRC with known amino acid sequence(RRLIQDAEYAARG) surrounding the phosphorylation site in pp60src (Krebs, E.G., 1985). rhIL-8 (E. Coli-expressed) challenge (1.0 μg/ml) increased [pPTK] by 190% over [sPTK] while decreasing (57%) [sPTK]. In rhIL-8 naive preparations, the enzyme activity was preferentially localized in [sPTK](141%/[pPTK]). Neutralizing polyclonal anti-rhIL-8 antibody(100 μg/ml) convincingly negated rhIL-8's ability to provoke [pPTK]. Interestingly, PD09859(MEK1 inhibitor, 10 μM) expanded [sPTK] by 616% and [pPTK] by 275%. Taken together, it is concluded within the context of this experimental paradigm that rhIL-8 exerted a stimulatory effect on [pPTK] and MEK1 inhibitor potentiated [PTK] induced by rhIL-8. Hence, it is proposed that interplay between PTK and MEK1 is involved in IL-8 associated modification of intracellular machinery and that the link of the two signal transducing enzyme systems may present a characteristic biochemical basis for cerebral reperfusion injury and related clinical manifestations. (Supported in part by Institute for Korean-American Studies, and American Heart Association national council #95009270)

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kim, S., Que, X., Russo, P. et al. INTERLEUKIN 8 (IL-8) STIMULATES AND MAP KINASE KINASE (MEK1) INHIBITOR POTENTIATES PROTEIN TYROSINE KINASE (PTK) ACTIVITY IN NEWBORN LAMB MIDDLE CEREBRAL ARTERIES (MCA) • 436. Pediatr Res 39, 75 (1996). https://doi.org/10.1203/00006450-199604001-00456

Download citation

Search