Sex differences in TLR2 and TLR4 expression and their effect on coxsackievirus-induced autoimmune myocarditis

Roberts, Brian; Moussawi, Mohamad; Huber, Sally A.

doi:10.1016/j.yexmp.2012.06.005

Cited by 44 publications

(29 citation statements)

References 32 publications

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“…[161][162][163] Moreover, animal studies suggest that sex differences in TLR signaling play an important role in differential susceptibility to CVB3-induced myocarditis in men and women. 21,164,165 The antiviral significance of IFNs has also been observed at the level of their gene targets. For example, IFN-inducible protein 10 is upregulated in viral-infected myocardium, and overexpression of this gene specifically in cardiomyocytes decreases virus titers leading to improved cardiac function.…”

Section: Immunopathogenesis Of Viral Myocarditismentioning

confidence: 99%

Myocarditis

Gabriel

Luo

Qiu

et al. 2016

Circulation Research

411

354

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Section: Immunopathogenesis Of Viral Myocarditismentioning

confidence: 99%

Myocarditis

Gabriel

Luo

Qiu

et al. 2016

Circulation Research

411

354

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“…Toll-like receptors (TLRs) can influence the severity of CVB3-induced myocarditis: mice deficient for TLR-3 developed more severe myocarditis than their wild type littermates, whereas TLR-4-deficient mice developed less severe myocarditis [68, 69]. Furthermore, expression of TLRs can occur gender dependently: elevated expression of TLR-4 in the macrophages of male mice contributed to mortalities in CVB3-infected animals, but the underlying mechanisms are unknown [70, 71]. In contrast, the roles played by certain cellular components of the innate immune system, such as gamma delta (γδ) T cells and natural killer (NK)-T cells, are more complex, in that γδ T cells and NK-T cells perform opposing functions (Fig.…”

Section: Pathogenesis Of Cvb3 Infectionmentioning

confidence: 99%

Intricacies of cardiac damage in coxsackievirus B3 infection: Implications for therapy

Massilamany

Gangaplara

Reddy

2014

International Journal of Cardiology

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Heart disease is the leading cause of death in humans, and myocarditis is one predominant cause of heart failure in young adults. Patients affected with myocarditis can develop dilated cardiomyopathy (DCM), a common reason for heart transplantation, which to date is the only viable option for combatting DCM. Myocarditis/DCM patients show antibodies to coxsackievirus B (CVB)3 and cardiac antigens, suggesting a role for CVB-mediated autoimmunity in the disease pathogenesis; however, a direct causal link remains to be determined clinically. Experimentally, myocarditis can be induced in susceptible strains of mice using the human isolates of CVB3, and the disease pathogenesis of postinfectious myocarditis resembles that of human disease, making the observations made in animals relevant to humans. In this review, we discuss the complex nature of CVB3-induced myocarditis as it relates to the damage caused by both the virus and the host's response to infection. Based on recent data we obtained in the mouse model of CVB3 infection, we provide evidence to suggest that CVB3 infection accompanies the generation of cardiac myosin-specific CD4 T cells that can transfer the disease to naïve recipients. The therapeutic implications of these observations are also discussed.

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“…TLRs are key receptors in the innate immune response to infectious microorganisms including lipids and nucleic acids, and they are activated by host-derived molecules and associated with ischemic inflammatory injury. 7 We do not know why the expression of TLR2 and TLR4 is different between male and female animals although Roberts et al 25 reported that in mice Coxsakie virus-induced autoimmune myocarditis, there is a sex difference in their expression. Cytokines can modulate TLR expression and sex hormones alter cytokine responses with estradiol and testosterone having distinct effects on proinflammatory and anti-inflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

PPARγ-Dependent and -Independent Inhibition of the HMGB1/TLR9 Pathway by Eicosapentaenoic Acid Attenuates Ischemic Brain Damage in Ovariectomized Rats

Sumiyoshi

Satomi

Kitazato

et al. 2015

Journal of Stroke and Cerebrovascular Diseases

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High mobility group box 1 (HMGB1) elevation after cerebral ischemia activates inflammatory pathways via receptors such as the receptor for advanced glycation end products (RAGE) and toll-like receptors (TLRs) and leads to brain damage. Eicosapentaenoic acid (EPA), a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, attenuates postischemic inflammation and brain damage in male animals. However, postischemic HMGB1 signaling and the effects of EPA on ovariectomized (OVX(+)) rats remain unclear. We hypothesized that EPA attenuates brain damage in OVX(+) rats via the inhibition of HMGB1 signaling in a PPARγ-dependent manner. Seven-week-old female Sprague-Dawley rats were divided into 3 groups; nonovariectomized (OVX(-)) rats and EPA-treated and EPA-untreated OVX(+) rats before cerebral ischemia induction. Another set of EPA-treated OVX(+) rats was injected with the PPARγ inhibitor GW9662. OVX(+) decreased the messenger RNA level of PPARγ and increased that of HMGB1, RAGE, TLR9, and tumor necrosis factor alpha (TNFα) in parallel with ischemic brain damage. EPA restored the PPARγ expression, downregulated the HMGB1 signal-related molecules, and attenuated the ischemic brain damage. Neither OVX(+) nor EPA affected the expression of TLR2 or TLR4. Interestingly, GW9662 partially abrogated the EPA-induced neuroprotection and the downregulation of RAGE and TLR9. In contrast, GW9662 did not affect HMGB1 or TNFα. These results suggest that EPA exerts PPARγ-dependent and PPARγ-independent effects on postischemic HMGB1/TLR9 pathway. The cortical infarct volume exacerbated by OVX(+) is associated with the upregulation of the HMGB1/TLR9 pathway. Suppression of this pathway may help to limit ischemic brain damage in postmenopausal women.

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Sex differences in TLR2 and TLR4 expression and their effect on coxsackievirus-induced autoimmune myocarditis

Cited by 44 publications

References 32 publications

Myocarditis

Myocarditis

Intricacies of cardiac damage in coxsackievirus B3 infection: Implications for therapy

PPARγ-Dependent and -Independent Inhibition of the HMGB1/TLR9 Pathway by Eicosapentaenoic Acid Attenuates Ischemic Brain Damage in Ovariectomized Rats

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