AI Article Synopsis
- Interleukin-5 (IL-5) activates beta(2)-integrin adhesion in human eosinophils through a time-dependent activation of ERK1/2 and p38alpha, which are important signaling proteins.
- Inhibiting ERK1/2 or src-family tyrosine kinases significantly reduces eosinophil adhesion and the activation of a key enzyme (cPLA(2)), while inhibition of p38 has no effect.
- The study suggests that Lyn, a src-family tyrosine kinase, may be a crucial upstream regulator of PI3K activation, leading to the necessary ERK1/2 phosphorylation for effective eosinophil adhesion induced by IL-5.
Article Abstract
We examined the mechanism by which interleukin (IL)-5 causes beta(2)-integrin adhesion of human eosinophils. IL-5 caused time-dependent activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38alpha in eosinophils as detected by their phosphorylation. Preincubation of eosinophils with U0126, a mitogen-activated protein kinase/ERK kinase inhibitor, suppressed IL-5-induced activation of cytosolic phospholipase A(2) (cPLA(2)) and eosinophil adhesion, and p38 inhibition by SB203580 had neither effect. ERK1/2 phosphorylation and eosinophil adhesion were blocked by inhibition of the src-family tyrosine kinase, Janus tyrosine kinase (JAK)2, or phosphoinositide-3 kinase (PI3K). Coimmunoprecipitation assay demonstrated that Lyn, a src-family tyrosine kinase, was constitutively associated with PI3K. Inhibition of src-tyrosine kinase but not JAK2 suppressed PI3K activation. Our data suggest that IL-5 induces beta(2)-integrin adhesion of human eosinophils by regulation of cPLA(2) activation caused by ERK1/2 phosphorylation. This phosphorylation results from activation of PI3K and protein tyrosine kinases. We also find that src-family tyrosine kinase, possibly Lyn, is the upstream kinase causing PI3K activation.
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