Inflammatory protein sPLA(2)-IIA abrogates TNFalpha-induced apoptosis in human astroglioma cells: Crucial role of ERK.

Abstract

Brain injury induces the expression of well-known cytokines, such as tumor necrosis factor-alpha (TNFalpha), and other, which functions are less understood, as secreted phospholipase A(2) group IIA (sPLA(2)-IIA). Since in pathological processes, cytokines function coordinately in networks, to further explore the actions of sPLA(2)-IIA in tumorigenesis, we investigated the effect of sPLA(2)-IIA in the presence of TNFalpha in human 1321N1 astrocytoma cells. In these cells, TNFalpha activates the apoptotic programme that is accompanied of cytoskeleton changes; however, simultaneous treatment with sPLA(2)-IIA prevents TNFalpha-mediated apoptosis and reverses the modification of the markers associated to this response. In fact, the mitogenic activity elicited by the phospholipase alone is preserved. This inhibitory effect is not found in other TNFalpha-mediated responses, even a functional cooperation is observed on COX-2 protein induction. The cross-talk between TNFalpha and sPLA(2)-IIA is associated with ERK activity since its pharmacological inhibition attenuates both synergistic and inhibitory responses. We have also observed that upon sPLA(2)-IIA stimulation, endogenous ERK has the capacity to bind and phosphorylate sequences present within the cytoplasmic domain of TNFR1/CD120a. These findings thus indicate that sPLA(2)-IIA and TNFalpha transduction pathways interact to modulate inflammatory responses and provide additional insights about the capacity of sPLA(2)-IIA to promote apoptosis resistance in astrocytoma cells.

• Authors: Elvira Ibeas, Lucía Fuentes, Rubén Martín, Marita Hernández, María Luisa Nieto
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1793 Issue 12 Pg. 1837-47 (Dec 2009) ISSN: 0006-3002 [Print] Netherlands
• PMID: 19850087 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Inflammation Mediators
• Receptors, Tumor Necrosis Factor, Type I
• Tumor Necrosis Factor-alpha
• Cyclooxygenase 2
• PTGS2 protein, human
• Extracellular Signal-Regulated MAP Kinases
• Group II Phospholipases A2

Topics

• Apoptosis
• Astrocytoma (genetics, metabolism)
• Cell Line, Tumor
• Cyclooxygenase 2 (biosynthesis, genetics)
• Enzyme Induction (drug effects, genetics)
• Extracellular Signal-Regulated MAP Kinases (genetics, metabolism)
• Group II Phospholipases A2 (genetics, metabolism, pharmacology)
• Humans
• Inflammation (genetics, metabolism)
• Inflammation Mediators (metabolism, pharmacology)
• MAP Kinase Signaling System
• Phosphorylation (drug effects, genetics)
• Protein Structure, Tertiary (genetics)
• Receptors, Tumor Necrosis Factor, Type I (genetics, metabolism)
• Tumor Necrosis Factor-alpha (genetics, metabolism, pharmacology)