Impairment of lysosomal functions by azithromycin and chloroquine contributes to anti-inflammatory phenotype

Nujić, Krunoslav; Banjanac, Mihailo; Munić, Vesna; Polančec, Denis; Haber, Vesna Eraković

doi:10.1016/j.cellimm.2012.09.007

Cited by 64 publications

(63 citation statements)

References 57 publications

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“…[8][9][10][86][87][88] The mechanism by which azithromycin shifts macrophages from the classically activated (M1) to the alternatively activated (M2) phenotype has not been completely elucidated [89][90][91] ; however, AP-1 activation and impairment of lysosomal functions may be probably involved. 92,93 These immunomodulatory properties contribute to the clinical efficacy of azithromycin in respiratory diseases, 25 whereas their relevance in neurodegenerative conditions has only been partially explored. The immunomodulatory effects of azithromycin result in a significant neuroprotection exerted by an i.p.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Properties of a Macrolide Antibiotic in a Mouse Model of Middle Cerebral Artery Occlusion: Characterization of the Immunomodulatory Effects and Validation of the Efficacy of Intravenous Administration

Amantea

Certo

Petrelli

et al. 2016

ASSAY and Drug Development Technologies

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Section: Discussionmentioning

confidence: 99%

Neuroprotective Properties of a Macrolide Antibiotic in a Mouse Model of Middle Cerebral Artery Occlusion: Characterization of the Immunomodulatory Effects and Validation of the Efficacy of Intravenous Administration

Amantea

Certo

Petrelli

et al. 2016

ASSAY and Drug Development Technologies

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“…It seems that impairement of lysosomal function by chloroquine leads to anti-inflammatory effects by inhibition of arachidonic acid release and prostaglandin E2 synthesis [56]. Cooper and colleagues considered that lysosomotropic effects of chloroquine are widely responsible for its anti-inflammatory properties (decreasing in production of proinflammatory cytokines such as: IFN-γ, TNF-α, IL-1, IL-6), but also emphasized the importance of non-lysosomotropic mechanisms (it was shown that chloroquine could inhibit TNF-α release in macrophages through inhibition of TNF-α mRNA synthesis) [10].…”

Section: Discussionmentioning

confidence: 99%

Acute Pretreatment with Chloroquine Attenuates Renal I/R Injury in Rats

et al. 2014

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BackgroundAcute kidney injury (AKI) still remains an unresolved problem in pharmacotherapy and renal inflammation is a major factor in its development. Chloroquine, a well-known antimalarial drug, posses pleitropic effects as well: antiinflammatory, anticoagulant and vascular actions. The effects of chloroquine on renal function may involve significant increase in urine flow rate, glomerular filtration rate and sodium excretion, as well as stimulation of nitric oxide synthase. However, its role in experimental models of renal I/R injury is unknown. We aimed to analyze the acute effects of a single-dose intravenous chloroquine administered at three different times in the experimental model of I/R injury in rat.MethodsRats were subjected to bilateral renal ischemia (45 min) followed by reperfusion with saline lasting 4 hours. Chloroquine was administered in doses of 0.3 mg/kg i.v. and 3 mg/kg i.v. 30 min before ischemia, 30 min before reperfusion and 5 min before reperfusion. Selected a hemodynamic, biochemical and morphological parameters were followed in the Sham-operated animals and rats subjected to I/R injury and pretreated with saline or chloroquine.ResultsChloroquine (0.3 and 3 mg/kg, i.v.) protected the I/R injured kidney in an U-shaped manner. Both doses were protective regarding biochemical and histological markers of the I/R injury (serum urea, creatinine and fractional excretion of sodium, as well as total histological score, tubular necrosis score and KIM-1 staining score) (P<0.05 vs. corresponding controls, i.e. rats subjected to I/R injury and treated with saline only). The protective effects of the lower dose of chloroquine were more profound. Time-related differences between pretreatments were not observed (P>0.05, all).ConclusionOur study shows for the first time that a single dose of chloroquine (0.3 mg/kg i.v.) could afford significant protection of the injured rat kidney.

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“…CQ/HCQ possess several mechanisms of action. For example, their accumulations in lysosomes and autophagic vacuoles inhibit the growth of intracellular bacteria and target them for degradation in intracellular organelles [12,14]; down-regulate proinflammatory cytokines (e.g., IL1, IL6 and TNFα) [15]; control TLR4 and NF-κB activation [16], and modulate antigen presentation [17]. Indeed, CQ/HCQ protect against many inflammatory diseases.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic effect of hydroxychloroquine on colorectal carcinogenesis in experimental murine colitis

Yao

Xie

et al. 2016

Biochemical Pharmacology

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Impairment of lysosomal functions by azithromycin and chloroquine contributes to anti-inflammatory phenotype

Cited by 64 publications

References 57 publications

Neuroprotective Properties of a Macrolide Antibiotic in a Mouse Model of Middle Cerebral Artery Occlusion: Characterization of the Immunomodulatory Effects and Validation of the Efficacy of Intravenous Administration

Neuroprotective Properties of a Macrolide Antibiotic in a Mouse Model of Middle Cerebral Artery Occlusion: Characterization of the Immunomodulatory Effects and Validation of the Efficacy of Intravenous Administration

Acute Pretreatment with Chloroquine Attenuates Renal I/R Injury in Rats

Therapeutic effect of hydroxychloroquine on colorectal carcinogenesis in experimental murine colitis

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