Regulation of CC-CKR2 chemokine receptor message degradation

During inflammatory and irnmuriological responses, leukocytes respond to external stimuli by altering the stability of cytokine and cytokine receptor messages. Cytokine messages containing A-U rich elements located in the 3' untranslated region (ARE) are the best studied examples of this process. AREs have been shown to act as targeting motifs for degradation of cytokine and transcription factor messages. Recently, we have observed that the IL-8 receptor messages. IL-8RA and B, also undergo changes in stability in response to the inflammatory stimulator LPS. To see if changes in stability is a common mechanism for regulation of chemokine receptor messages we explored whether the stability of the beta chemokine receptor messages for CC-CKR1 and CC-CKR2 are also regulated by LPS. We found that LPS induces a rapid loss of steady state levels of CC-CKR1 and CC-CKR2 message. Much to our surprise the addition of ACT D along with LPS increased levels of CCCKR2 message. By delaying the addition of ACT D, the stabilizing effect of ACT D was reversed, resulting in the accelerated loss of CC-CKR2 message. Addition of cyclohexamide at the time of LPS treatment also increased CC-CKR2 message levels. We conclude from these data that LPS stimulates CC-CKR2 message degradation partially through a transcriptionally dependent step. Furthermore, LPS stimulated degradation is specific for a class of messages to which CC-CKR2 belongs because the message for MIP-la, which contains an ARE motif, was stabilized by LPS stimulation.