Dataset Information

IRF3 and IRF7 mediate neovascularization via inflammatory cytokines.

ABSTRACT:

Objective

To elucidate the role of interferon regulatory factor (IRF)3 and IRF7 in neovascularization.

Methods

Unilateral hind limb ischaemia was induced in Irf3^-/- , Irf7^-/- and C57BL/6 mice by ligation of the left common femoral artery. Post-ischaemic blood flow recovery in the paw was measured with laser Doppler perfusion imaging. Soleus, adductor and gastrocnemius muscles were harvested to investigate angiogenesis and arteriogenesis and inflammation.

Results

Post-ischaemic blood flow recovery was decreased in Irf3^-/- and Irf7^-/- mice compared to C57BL/6 mice at all time points up to and including sacrifice, 28 days after surgery (t28). This was supported by a decrease in angiogenesis and arteriogenesis in soleus and adductor muscles of Irf3^-/- and Irf7^-/- mice at t28. Furthermore, the number of macrophages around arterioles in adductor muscles was decreased in Irf3^-/- and Irf7^-/- mice at t28. In addition, mRNA expression levels of pro-inflammatory cytokines (tnf?, il6, ccl2) and growth factor receptor (vegfr2), were decreased in gastrocnemius muscles of Irf3^-/- and Irf7^-/- mice compared to C57BL/6 mice.

Conclusion

Deficiency of IRF3 and IRF7 results in impaired post-ischaemic blood flow recovery caused by attenuated angiogenesis and arteriogenesis linked to a lack of inflammatory components in ischaemic tissue. Therefore, IRF3 and IRF7 are essential regulators of neovascularization.

SUBMITTER: Simons KH

PROVIDER: S-EPMC6533520 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

IRF3 and IRF7 mediate neovascularization via inflammatory cytokines.

Simons Karin H KH de Vries Margreet R MR de Jong Rob C M RCM Peters Hendrika A B HAB Jukema J Wouter JW Quax Paul H A PHA

Journal of cellular and molecular medicine 20190401 6

<h4>Objective</h4>To elucidate the role of interferon regulatory factor (IRF)3 and IRF7 in neovascularization.<h4>Methods</h4>Unilateral hind limb ischaemia was induced in Irf3<sup>-/-</sup> , Irf7<sup>-/-</sup> and C57BL/6 mice by ligation of the left common femoral artery. Post-ischaemic blood flow recovery in the paw was measured with laser Doppler perfusion imaging. Soleus, adductor and gastrocnemius muscles were harvested to investigate angiogenesis and arteriogenesis and inflammation.<h4>R ...[more]

PMID: 30932349

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Project description:ObjectiveTo investigate the correlations between aqueous concentrations of interleukin 1?, 6, 8, 10, 12p (IL-1?, IL-6, IL-8, IL-10, IL-12p), and tumor necrosis factor ? (TNF-?) and the parameters of macular edema acquired by optical coherence tomography (OCT) in patients with choroidal neovascularization.MethodsIL-1?, IL-6, IL-8, IL-10, IL-12p, and TNF-? in the aqueous humor samples of 17 patients with exudative age-related macular degeneration (AMD), ten patients with pathological myopia (PM), seven patients with idiopathic choroidal neovascularization (CNV), and 14 patients with cataract and idiopathic epiretinal membrane or macular hole in the control group were measured with cytometric bead array. The maximum macular thickness and macular volume within 1 mm, 3 mm, and 6 mm were measured with OCT.ResultsIn the CNV groups, the aqueous levels of IL-6 and IL-8 were significantly associated with macular volume within 6 mm (p=0.011, p=0.008, respectively), while IL-1?, IL-10, IL-12p, and TNF-? showed no significant correlation with either the maximum macular thickness or the macular volume. By further selecting patients with CNV who had accepted their last intravitreal injection of bevacizumab within 3 months, the level of IL-6 still significantly correlated with the maximum macular thickness (p=0.019) and macular volume within 1 mm (p=0.018), 3 mm (p=0.018), and 6 mm (p=0.022). In patients with exudative AMD, the level of IL-6 was significantly associated with the maximum macular thickness (p=0.025) and macular volume within 1 mm (p=0.025), 3 mm (p=0.006), and 6 mm (p=0.002). The aqueous level of all cytokines did not vary significantly between the CNV patients who had accepted their last intravitreal injection of bevacizumab within 3 months and the other patients, nor was a difference found among patients with exudative AMD, PM, and idiopathic CNV, and the control group.ConclusionsIntraocular concentrations of IL-6 and IL-8 (particularly IL-6) are significantly associated with the volume of macular edema in patients with CNV. However, intravitreal injection of antivascular endothelial growth factor drugs did not change the intraocular level of these inflammation cytokines.

Dataset Information

IRF3 and IRF7 mediate neovascularization via inflammatory cytokines.

Objective

Methods

Results

Conclusion

Publications

IRF3 and IRF7 mediate neovascularization via inflammatory cytokines.

Similar Datasets

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