* Laboratorio di Patologia Vascolare, Istituto Dermopatico dell’Immacolata-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy; and
Department of Experimental Medicine and Pathology, University of Rome, "La Sapienza," Italy
Correspondence: Monica Napolitano, M.D., Ph.D., Laboratorio di Patologia Vascolare, Istituto Dermopatico dell’Immacolata-IRCCS, 00167, Via Monti di Creta 104, Rome, Italy. E-mail: m.napolitano{at}idi.it
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.
Key Words: viral • kinases • thymocytes • cell death
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