Chemokine receptor 4 (CXCR4) blockade enhances resistance to bacterial internalization in RAW264.7 cells and AMD3100, a CXCR4 antagonist, attenuates susceptibility to Brucella abortus 544 infection in a murine model

Reyes, Alisha Wehdnesday Bernardo; Arayan, Lauren Togonon; Huy, Nguyen Tien; Vu, Son Hai; Kang, Chang Keun; Min, Wongi; Lee, Hu Jang; Lee, John Hwa; Kim, Suk

doi:10.1016/j.vetmic.2019.108402

Cited by 8 publications

(2 citation statements)

References 34 publications

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“…The findings of the present study confirm the research that revealed that early TB spread of M.tb infection was associated with the onset of antimycobacterial immunity (31). The defect in the granuloma may be recapitulated by pharmacological inhibitors of CXCR4, such as motixafortide (BKT140 4-fluorobenzoyl) (32). Chemotaxis depends heavily on CXCR4.…”

Section: Discussionsupporting

confidence: 88%

Anti‑CXCR4 chemokine receptor, motixafortide, as an adjunct treatment with anti‑TB drugs decreases the bacterial burden by improving drug distribution

Davuluri

Singh

et al. 2023

World Acad Sci J

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C-X-C motif chemokine receptor 4 (CXCR4) is involved in the migration of bloodcells and the formation of blood vessels. It is expressed on blood cells and other immune cells such as dendritic cells and lymphocytes. Mycobacterium tuberculosis (M. tb) induces granuloma-associated angiogenesis, which is associated with the mycobacterial-induced expression of CXCR4. However, the significance of pathogen-induced angiogenesis remains elusive. The aim of the present study was to investigate the role and expression levels of CXCR4 during M.tb infection. To inhibit CXCR4, motixafortide, an antagonist for CXCR4, was used. The effect of motixafortide on M.tb dissemination, attenuation of bacterial growth and immunological responses in a guinea pig animal model was extensively studied using immunohistochemistry, as well as immunological and colony enumeration assays. The pharmacokinetics of first-line drugs in plasma, the lungs, and granuloma were evaluated following the inhibition of the expression of CXCR4 through motixafortide therapy. The results revealed that CXCR4 stimulation induced the expression of vascular endothelial growth factor-A (VEGFA) in M.tb-infected guinea pigs. Improvement in the pharmacokinetic parameters and early bacterial clearance in the spleen were observed in motixafortide anti-tuberculosis (TB) drug therapy in contrast to therapy with first-line drugs alone. G ranulomatous capture of first line drugs combined with motixafortide may have significant implications through different mechanisms. In the present study, it was demonstrated that CXCR4 inhibitors may be used as a therapeutic strategy to combat granuloma-angiogenesis by interfering with VEGFA signalling and controlling the spread of M.tb infection.

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Section: Discussionsupporting

confidence: 88%

Anti‑CXCR4 chemokine receptor, motixafortide, as an adjunct treatment with anti‑TB drugs decreases the bacterial burden by improving drug distribution

Davuluri

Singh

et al. 2023

World Acad Sci J

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“…A synthetic chiral compound of NDGA, nordy, was found to diminish the expression of chemokine receptor 4 (CXCR4) and formyl peptide receptor (FPR) in glioma cells, both are G-protein-coupled receptor (GPCR), which might indirectly suggest the anticancer activities of NDGA [ 15 , 16 ]. We also recently reported the beneficial effects of CXCR4 and FPR2 inhibition in the progression of B. abortus 544 infection [ 17 , 18 ]. Here we explore the effect of NDGA and M 4 N on B. abortus 544 infection in a murine professional phagocyte cell line using RAW264.7 cells as well as in a murine model using ICR mice.…”

Section: Introductionmentioning

confidence: 99%

The In Vitro and In Vivo Effect of Lipoxygenase Pathway Inhibitors Nordihydroguaiaretic Acid and Its Derivative Tetra-O-methyl Nordihydroguaiaretic Acid againstBrucella abortus544

Reyes

Kim

Huy

et al. 2022

J. Microbiol. Biotechnol.

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This study investigated the contribution of lipoxygenase (LOX) inhibitors, nordihydroguaiaretic acid (NDGA), tetra-O-methyl nordihydroguaiaretic acid (M 4 N) and zileuton (ZIL), and thromboxane A2 (TXA 2 ) inhibitor 4,5-diphenylimidazole (DPI) in the proliferation of Brucella abortus infection. None of the compounds affected the uptake of Brucella into the macrophages. We determined the effect of neutralizing leukotriene B4 (LTB4) receptor and showed that the uptake of the bacteria was inhibited at 30 min post-infection. M 4 N treatment attenuated intracellular survival of Brucella at 2 h post-incubation but it was not observed in the succeeding time points. DPI treatment showed reduced survival of Brucella at 24 h post-incubation while blocking LTB4 receptor was observed to have a lower intracellular growth at 48 h post-incubation suggesting different action of the inhibitors in the course of the survival of Brucella within the cells. Reduced proliferation of the bacteria in the spleens of mice was observed in animals treated with ZIL or DPI. Increased serum cytokine level of TNF-α and MCP-1 was observed in mice treated with M 4 N or ZIL while a lower IFN-γ level in ZIL-treated mice and a higher IL-12 serum level in DPI-treated mice were observed at 7 d postinfection. At 14 d post-infection, ZIL-treated mice displayed reduced serum level of IL-12 and IL-10. Overall, inhibition of 5-LOX or TXA 2 or a combination therapy promises a potential alternative therapy against B. abortus infection. Furthermore, strong ligands for LTB4 receptor could also be a good candidate for the control of Brucella infection.

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Nile tilapia CXCR4, the receptor of chemokine CXCL12, is involved in host defense against bacterial infection and chemotactic activity

Gao

Yan

et al. 2021

Developmental & Comparative Immunology

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Chemokine receptor 4 (CXCR4) blockade enhances resistance to bacterial internalization in RAW264.7 cells and AMD3100, a CXCR4 antagonist, attenuates susceptibility to Brucella abortus 544 infection in a murine model

Cited by 8 publications

References 34 publications

Anti‑CXCR4 chemokine receptor, motixafortide, as an adjunct treatment with anti‑TB drugs decreases the bacterial burden by improving drug distribution

Anti‑CXCR4 chemokine receptor, motixafortide, as an adjunct treatment with anti‑TB drugs decreases the bacterial burden by improving drug distribution

The In Vitro and In Vivo Effect of Lipoxygenase Pathway Inhibitors Nordihydroguaiaretic Acid and Its Derivative Tetra-O-methyl Nordihydroguaiaretic Acid againstBrucella abortus544

Nile tilapia CXCR4, the receptor of chemokine CXCL12, is involved in host defense against bacterial infection and chemotactic activity

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