Premium
The chemokine receptor CCR8 mediates rescue from dexamethasone‐induced apoptosis via an ERK‐dependent pathway
Author(s) -
Spinetti Gaia,
Bernardini Giovanni,
Camarda Grazia,
Mangoni Antonella,
Santoni Angela,
Capogrossi Maurizio C.,
Napolitano Monica
Publication year - 2003
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0302105
Subject(s) - biology , chemokine receptor , chemokine , ccl17 , cancer research , cc chemokine receptors , c c chemokine receptor type 6 , microbiology and biotechnology , immunology , inflammation
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 apoptois 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.