The chemokine receptor CCR8 mediates rescue from dexamethasone-induced apoptosis via an ERK-dependent pathway.

Abstract

Several chemokines have been shown to regulate cellular apoptosis following discrete stimuli. It was previously demonstrated that the CC chemokine CCL1 (I-309) rescues thymic lymphoma cells from apoptosis by unknown mechanisms. The aim of our study was to characterize the role of the CC chemokine receptor 8 (CCR8), the only described receptor for CCL1, in the rescue of murine thymic lymphoma cells and murine thymocytes from dexamethasone (dex)-induced apoptosis. We show here that the CCR8-restricted agonist Kaposi sarcoma-associated herpesvirus-encoded chemokine viral macrophage-inflammatory protein-1 (vMIP-1) rescues thymic lymphoma cells from dex-induced apoptosis, similar to CCL1, and that such rescue is extracellular-regulated kinase-dependent. Although it has been hypothesized that the rescuing effect of CCL1 from apoptosis could be CCR8-mediated, here, we formally demonstrate the role of such receptor as its selective antagonist encoded by the MC148 gene of molluscum contagiosum virus MC148/vMCC-I inhibits v-MIP-1- and CCL1-induced rescue activity. In addition, CCR8 ligands inhibit dex-induced apoptosis of murine thymocytes with potential implications for thymic selection.

• Authors: Gaia Spinetti, Giovanni Bernardini, Grazia Camarda, Antonella Mangoni, Angela Santoni, Maurizio C Capogrossi, Monica Napolitano
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 73 Issue 1 Pg. 201-7 (Jan 2003) ISSN: 0741-5400 [Print] United States
• PMID: 12525579 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCL1 protein, human
• CCR8 protein, human
• Ccl1 protein, mouse
• Chemokine CCL1
• Chemokines, CC
• MC148 protein, poxvirus molluscum contagiosum
• Macrophage Inflammatory Proteins
• Receptors, CCR8
• Receptors, Chemokine
• Viral Proteins
• vMIP-1 protein, Human herpesvirus 8
• Dexamethasone
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Apoptosis (drug effects)
• Binding Sites
• Calcium Signaling
• Chemokine CCL1
• Chemokines, CC (antagonists & inhibitors, metabolism)
• Chemotaxis, Leukocyte
• Dexamethasone (pharmacology)
• Female
• Humans
• Lymphoma, T-Cell (pathology)
• Macrophage Inflammatory Proteins (pharmacology)
• Mice
• Mitogen-Activated Protein Kinases (physiology)
• Receptors, CCR8
• Receptors, Chemokine (agonists, physiology)
• Signal Transduction
• Thymus Gland (cytology)
• Viral Proteins