MicroRNA-424 regulates the expression of CX3CL1 (fractalkine) in human microvascular endothelial cells during Rickettsia rickettsii infection
Cytokines and chemokines trigger complex intracellular signaling through specific receptors to mediate immune cell recruitment and activation at the sites of infection. CX3CL1 (Fractalkine), a membrane-bound chemokine also capable of facilitating intercellular interactions as an adhesion molecule, c...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-03-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580820302077 |
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| author | Abha Sahni Hema P. Narra Sanjeev K. Sahni |
| author_facet | Abha Sahni Hema P. Narra Sanjeev K. Sahni |
| author_sort | Abha Sahni |
| collection | DOAJ |
| description | Cytokines and chemokines trigger complex intracellular signaling through specific receptors to mediate immune cell recruitment and activation at the sites of infection. CX3CL1 (Fractalkine), a membrane-bound chemokine also capable of facilitating intercellular interactions as an adhesion molecule, contributes to host immune responses by virtue of its chemoattractant functions. Published studies have documented increased CX3CL1 expression in target tissues in a murine model of spotted fever rickettsiosis temporally corresponding to infiltration of macrophages and recovery from infection. Because pathogenic rickettsiae primarily target vascular endothelium in the mammalian hosts, we have now determined CX3CL1 mRNA and protein expression in cultured human microvascular endothelial cells (HMECs) infected in vitro with Rickettsia rickettsii. Our findings reveal 15.5 ± 4.0-fold and 12.3 ± 2.3-fold increase in Cx3cl1 mRNA expression at 3 h and 24 h post-infection, coinciding with higher steady-state levels of the corresponding protein in comparison to uninfected HMECs. Since CX3CL1 is a validated target of microRNA (miR)-424-5p (miR-424) and our earlier findings demonstrated robust down-regulation of miR-424 in R. rickettsii-infected HMECs, we further explored the possibility of regulation of CX3CL1 expression during rickettsial infection by miR-424. As expected, R. rickettsii infection resulted in 87 ± 5% reduction in miR-424 expression in host HMECs. Interestingly, a miR-424 mimic downregulated R. rickettsii-induced expression of CX3CL1, whereas an inhibitor of miR-424 yielded a converse up-regulatory effect, suggesting miR-424-mediated regulation of CX3CL1 during infection. Together, these findings provide the first evidence for the roles of a host microRNA in the regulation of an important bifunctional chemokine governing innate immune responses to pathogenic rickettsiae. |
| first_indexed | 2024-12-14T05:55:55Z |
| format | Article |
| id | doaj.art-f6157ef304094fea9b0125dc75bde719 |
| institution | Directory Open Access Journal |
| issn | 2405-5808 |
| language | English |
| last_indexed | 2024-12-14T05:55:55Z |
| publishDate | 2021-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj.art-f6157ef304094fea9b0125dc75bde7192022-12-21T23:14:35ZengElsevierBiochemistry and Biophysics Reports2405-58082021-03-0125100897MicroRNA-424 regulates the expression of CX3CL1 (fractalkine) in human microvascular endothelial cells during Rickettsia rickettsii infectionAbha Sahni0Hema P. Narra1Sanjeev K. Sahni2Corresponding author. Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0609, USA.; Department of Pathology, University of Texas Medical Branch, Galveston, TX, 77555-0609, USADepartment of Pathology, University of Texas Medical Branch, Galveston, TX, 77555-0609, USADepartment of Pathology, University of Texas Medical Branch, Galveston, TX, 77555-0609, USACytokines and chemokines trigger complex intracellular signaling through specific receptors to mediate immune cell recruitment and activation at the sites of infection. CX3CL1 (Fractalkine), a membrane-bound chemokine also capable of facilitating intercellular interactions as an adhesion molecule, contributes to host immune responses by virtue of its chemoattractant functions. Published studies have documented increased CX3CL1 expression in target tissues in a murine model of spotted fever rickettsiosis temporally corresponding to infiltration of macrophages and recovery from infection. Because pathogenic rickettsiae primarily target vascular endothelium in the mammalian hosts, we have now determined CX3CL1 mRNA and protein expression in cultured human microvascular endothelial cells (HMECs) infected in vitro with Rickettsia rickettsii. Our findings reveal 15.5 ± 4.0-fold and 12.3 ± 2.3-fold increase in Cx3cl1 mRNA expression at 3 h and 24 h post-infection, coinciding with higher steady-state levels of the corresponding protein in comparison to uninfected HMECs. Since CX3CL1 is a validated target of microRNA (miR)-424-5p (miR-424) and our earlier findings demonstrated robust down-regulation of miR-424 in R. rickettsii-infected HMECs, we further explored the possibility of regulation of CX3CL1 expression during rickettsial infection by miR-424. As expected, R. rickettsii infection resulted in 87 ± 5% reduction in miR-424 expression in host HMECs. Interestingly, a miR-424 mimic downregulated R. rickettsii-induced expression of CX3CL1, whereas an inhibitor of miR-424 yielded a converse up-regulatory effect, suggesting miR-424-mediated regulation of CX3CL1 during infection. Together, these findings provide the first evidence for the roles of a host microRNA in the regulation of an important bifunctional chemokine governing innate immune responses to pathogenic rickettsiae.http://www.sciencedirect.com/science/article/pii/S2405580820302077CX3CL1 (fractalkine)Endothelial cellsmicroRNA-424-5p (miR-424)Rickettsia |
| spellingShingle | Abha Sahni Hema P. Narra Sanjeev K. Sahni MicroRNA-424 regulates the expression of CX3CL1 (fractalkine) in human microvascular endothelial cells during Rickettsia rickettsii infection Biochemistry and Biophysics Reports CX3CL1 (fractalkine) Endothelial cells microRNA-424-5p (miR-424) Rickettsia |
| title | MicroRNA-424 regulates the expression of CX3CL1 (fractalkine) in human microvascular endothelial cells during Rickettsia rickettsii infection |
| title_full | MicroRNA-424 regulates the expression of CX3CL1 (fractalkine) in human microvascular endothelial cells during Rickettsia rickettsii infection |
| title_fullStr | MicroRNA-424 regulates the expression of CX3CL1 (fractalkine) in human microvascular endothelial cells during Rickettsia rickettsii infection |
| title_full_unstemmed | MicroRNA-424 regulates the expression of CX3CL1 (fractalkine) in human microvascular endothelial cells during Rickettsia rickettsii infection |
| title_short | MicroRNA-424 regulates the expression of CX3CL1 (fractalkine) in human microvascular endothelial cells during Rickettsia rickettsii infection |
| title_sort | microrna 424 regulates the expression of cx3cl1 fractalkine in human microvascular endothelial cells during rickettsia rickettsii infection |
| topic | CX3CL1 (fractalkine) Endothelial cells microRNA-424-5p (miR-424) Rickettsia |
| url | http://www.sciencedirect.com/science/article/pii/S2405580820302077 |
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