Shedding of the soluble IL-6 receptor is triggered by Ca2+ mobilization, while basal release is predominantly the product of differential mRNA splicing in THP-1 cells.

作者: Simon A. Jones , Sankichi Horiuchi , Daniela Novick , Naoki Yamamoto , Gerald M. Fuller

DOI: 10.1002/(SICI)1521-4141(199811)28:11<3514::AID-IMMU3514>3.0.CO;2-T

关键词:

摘要: The soluble IL-6 receptor (sIL-6R) is generated through either proteolytic shedding of the cognate (PC-sIL-6R), or released as product differential mRNA splicing (DS-sIL-6R). Using monocytic THP-1 cells, we demonstrate that both mechanisms are independently regulated, and each process contributes to sIL-6R production. Shedding IL-6R was activated by Ca2+ ionophore, ionomycin, inhibited TNF-alpha protease inhibitor (TAPI). In contrast, basal release unaffected depletion largely insensitive TAPI. Moreover, although inactivated serum starvation, non-stimulated production remained intact. Basal via shown inhibitory action brefeldin A an enzyme-linked immunosorbent assay specific for DS-sIL-6R. Release this isoform ionomycin TAPI, indicating mobilization activates PC-sIL-6R generation, but not divergent control these isoforms indicates they may influence inflammatory response.

参考文章(30)
A K Samanta, J J Oppenheim, K Matsushima, Interleukin 8 (monocyte-derived neutrophil chemotactic factor) dynamically regulates its own receptor expression on human neutrophils. Journal of Biological Chemistry. ,vol. 265, pp. 183- 189 ,(1990) , 10.1016/S0021-9258(19)40213-5
M Honda, H Suzuki, T Tokunaga, T Kishimoto, K Yasukawa, T Saito, Y Osugi, M Cheng, S Yamamoto, Human soluble IL-6 receptor: its detection and enhanced release by HIV infection. Journal of Immunology. ,vol. 148, pp. 2175- 2180 ,(1992)
L Graeve, J Müllberg, P C Heinrich, S Rose-John, E Dittrich, E Mehl, W Oberthür, F Lottspeich, The soluble human IL-6 receptor. Mutational characterization of the proteolytic cleavage site. Journal of Immunology. ,vol. 152, pp. 4958- 4968 ,(1994)
J Müllberg, D Cosman, C Otten-Evans, S Rose-John, K M Mohler, F H Durie, R A Black, M R Alderson, A metalloprotease inhibitor blocks shedding of the IL-6 receptor and the p60 TNF receptor. Journal of Immunology. ,vol. 155, pp. 5198- 5205 ,(1995)
A Pandiella, J Massagué, Multiple signals activate cleavage of the membrane transforming growth factor-alpha precursor. Journal of Biological Chemistry. ,vol. 266, pp. 5769- 5773 ,(1991) , 10.1016/S0021-9258(19)67662-3
S Rose-John, P C Heinrich, Soluble receptors for cytokines and growth factors: generation and biological function Biochemical Journal. ,vol. 300, pp. 281- 290 ,(1994) , 10.1042/BJ3000281
J Potempa, J Pryjma, J Travis, S Rose-John, J Cichy, Oncostatin M stimulates the expression and release of the IL-6 receptor in human hepatoma HepG2 cells. Journal of Immunology. ,vol. 159, pp. 5648- 5653 ,(1997)
H. Hirota, K. Yoshida, T. Kishimoto, T. Taga, CONTINUOUS ACTIVATION OF GP130, A SIGNAL-TRANSDUCING RECEPTOR COMPONENT FOR INTERLEUKIN 6-RELATED CYTOKINES, CAUSES MYOCARDIAL HYPERTROPHY IN MICE Proceedings of the National Academy of Sciences of the United States of America. ,vol. 92, pp. 4862- 4866 ,(1995) , 10.1073/PNAS.92.11.4862
V Modur, Y Li, G A Zimmerman, S M Prescott, T M McIntyre, Retrograde inflammatory signaling from neutrophils to endothelial cells by soluble interleukin-6 receptor alpha. Journal of Clinical Investigation. ,vol. 100, pp. 2752- 2756 ,(1997) , 10.1172/JCI119821