Difference between revisions of "Part:BBa K1993002"

Latest revision as of 17:55, 23 October 2020

CXCR1

Chemokine receptors are receptors found on the surface of certain cells that interact with chemokines. They have a 7-transmembrane (7-TM) structure and couple to G-protein for signal transduction within a cell. [1] (Figure 1) Following interaction with their specific chemokine ligands, chemokine receptors trigger a flux intracellular calcium (Ca2+) ions, initiate chemotaxis and guide the cell to a desired location. (Figure 2)

Figure 1. typical structure of a chemokine receptor.

Figure 2. the mechanism of interaction between a chemokine and a chemokine receptor.

Under the circumstances of inflammation, various kinds of cytokines, including chemokines, are released by the lesions. Guided by the chemokines, cells expressing chemokine receptors move towards the lesions where they can function better.[2] What’s more, different diseases would release different pools of chemokines, which would recruit different effector cells. See our disease table-chemokine

Based on the chemotaxis theory, in order to enhance the homing ability of our marvelous mesenchymal stem cells (MSCs) due to lack of enough chemokine receptors on their cell surface, we, SYSU-MEDICINE, had constructed a series of chemokine receptors that corresponding to different inflammatory diseases as far as possible. Among which, CXCL6 is a significant chemokine (CXCR1 is its chemokine receptor) in Inflammatory Bowel Disease(IBD). See our disease table-chemokine

We acquired this gene from peripheral mononuclear blood cells (PMBCs) and purified it. (Figure 3) Then we constructed it under the control of EF-1α by Gateway technology. (Figure 4)

Figure 3 Purification of CXCR1

Figure 4 EF-1α-CXCR1

Then, we tested the chemotaxis of engineered MSCs by conducting Transwell assay against CXCL6. To our excitement, our engineered MSCs had improved their homing ability with chemokine receptor CXCR1(Figure 5).

Figure 5. Transwell Assay of CXCR1.

MIT_MAHE 2020

Summary

Chemokine receptors are receptors found on the surface of certain cells that interact with chemokines. They have a 7-transmembrane (7-TM) structure and couple to G-protein for signal transduction within a cell. Following interaction with their specific chemokine ligands, chemokine receptors trigger a flux intracellular calcium (Ca2+) ions, initiate chemotaxis and guide the cell to a desired location. Under the circumstances of inflammation, various kinds of cytokines, including chemokines, are released by the lesions. Guided by the chemokines, cells expressing chemokine receptors move towards the lesions where they can function better. This protein is a receptor for IL-8.

References

[1]Allen, Samantha J.; Crown, Susan E.; Handel, Tracy M. (2007-01-01). "Chemokine: receptor structure, interactions, and antagonism". Annual Review of Immunology. 25: 787–820.

[2] Griffith J W, Sokol C L, Luster A D. Chemokines and chemokine receptors: positioning cells for host defense and immunity.[J]. Annual Review of Immunology, 2014, 32(1):659-702.

[3] Firestein G. S. (2003). Evolving concepts of rheumatoid arthritis. Nature, 423(6937), 356–361. https://doi.org/10.1038/nature01661

[4] Firestein G. S. (2005). Immunologic mechanisms in the pathogenesis of rheumatoid arthritis. Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 11(3 Suppl), S39–S44. https://doi.org/10.1097/01.rhu.0000166673.34461.33

[5] Moreland, L. W., Baumgartner, S. W., Schiff, M. H., Tindall, E. A., Fleischmann, R. M., Weaver, A. L., Ettlinger, R. E., Cohen, S., Koopman, W. J., Mohler, K., Widmer, M. B., & Blosch, C. M. (1997). Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. The New England journal of medicine, 337(3), 141–147. https://doi.org/10.1056/NEJM199707173370301

[6] Jiang, Y., Genant, H. K., Watt, I., Cobby, M., Bresnihan, B., Aitchison, R., & McCabe, D. (2000). A multicenter, double-blind, dose-ranging, randomized, placebo-controlled study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis: radiologic progression and correlation of Genant and Larsen scores. Arthritis and rheumatism, 43(5), 1001–1009. https://doi.org/10.1002/1529-0131(200005)43:5<1001::AID-ANR7>3.0.CO;2-P"

Sequence and Features