Regulation of CCR2 chemokine receptor mRNA stability
| Autor: | A Biragyn, Luoling Xu, J M Wang, Longsi Ran, Mark E. DeVries, Joseph D. Andrews, C Kong, R Rahimpour, David J. Kelvin |
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| Rok vydání: | 1997 |
| Předmět: |
Lipopolysaccharides
CCR2 Transcription Genetic Receptors CCR2 Immunology C-C chemokine receptor type 6 Biology Sensitivity and Specificity Monocytes Cell Line Chemokine receptor Drug Stability Humans Immunology and Allergy CXCL11 RNA Messenger Protein Synthesis Inhibitors Adenine Cell Biology Stimulation Chemical Cell biology CXCL2 Dactinomycin XCL2 Receptors Chemokine CCL25 CCL21 |
| Zdroj: | Journal of Leukocyte Biology. 62:653-660 |
| ISSN: | 1938-3673 0741-5400 |
| DOI: | 10.1002/jlb.62.5.653 |
| Popis: | During inflammatory and immunological responses, leukocytes respond to external stimuli by altering the stability of cytokine and cytokine receptor messages. Change in message stability is an effective mechanism for rapidly regulating steady state levels of mRNA. 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. We have recently observed that the interleukin-8 (IL-8) receptor messages, IL-8RA and B (CXCR1 and CXCR2), also undergo changes in stability in response to the inflammatory stimulator lipopolysaccharide (LPS). To determine whether regulation of message stability is a common mechanism for modulation of chemokine receptor mRNA we explored whether the stability of the CC chemokine receptor message for CCR2 (monocyte chemotactic protein-1 receptor) is also regulated by LPS. We found that LPS induces a rapid loss of steady state levels of CCR2 message through message degradation. Furthermore, LPS stimulated the decay of Poly(A) CCR2 mRNA faster than total CCR2 RNA, indicating that deadenylation is the first step in LPS-induced CCR2 RNA degradation. We conclude from these experiments that LPS stimulates the rapid degradation of CCR2 messages through a two-step process, deadenylation followed by degradation of the message body. In contrast to the results obtained for CCR2 mRNA, macrophage inflammatory protein-1α messages, which contain an ARE motif, were stabilized by LPS stimulation, indicating that chemokine and chemokine receptor mRNA stability are regulated by different and opposing mechanisms. |
| Databáze: | OpenAIRE |
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