Tacrolimus, but not Cyclosporine A, significantly increases expression of ICAM-1 and IFN-? in the NOD mouse

Papaccio, Gianpaolo; Latronico, Michael V.G.; Graziano, Antonio; Lanza, Alessandro; Pedullà, Marcella

doi:10.1002/jcb.1092

Cited by 5 publications

(2 citation statements)

References 26 publications

(27 reference statements)

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“…In the present study, we found a significant reduction in Akt and its downstream p70S6K as well as ICAM‐1 with NCL intervention. In the contrary, it was also evidenced that TAC application significantly elevated the levels of ICAM‐1 as compared with IMQ and these findings are consistent with the previous reports (Papaccio, Latronico, Graziano, Lanza, & Pedullà, ).…”

Section: Discussionsupporting

confidence: 91%

Repurposing an old drug for new use: Niclosamide in psoriasis‐like skin inflammation

Thatikonda

Pooladanda

Godugu

2019

Journal Cellular Physiology

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Drug discovery is an onerous, extremely expensive, and time‐consuming process. Instead, drug repurposing is an attractive strategy for exploiting novel indications for a drug beyond its original use. The untapped potential of drug repurposing compensates the barriers associated with the drug discovery pipeline. Psoriasis is an autoimmune skin disease, where hyperproliferation of keratinocytes and exaggerated immune responses are the important hallmarks of the disease. Extensive in vitro and preclinical research has demonstrated that niclosamide was found to exert potent anticancer and anti‐inflammatory properties by targeting STAT3, p65 NF‐κB, and NFATc‐1 signaling paradigm with minimal host toxicity. From the disease perspective, the static intracellular molecular network in both cancer and psoriasis share overlapping pathological features in terms of hyperproliferation and chronic inflammation, which is mediated by the aforementioned signaling cascade. The plausible mechanistic relevance has prompted us to investigate the implementation of niclosamide for repositioning in psoriasis. Our in vitro and in vivo findings suggest that niclosamide inhibits keratinocytes hyperproliferation by reactive oxygen species‐mediated apoptosis through the loss of mitochondrial membrane potential, cell cycle arrest at Sub G1 phase, and DNA fragmentation. Furthermore, niclosamide treatment resulted in abrogation of lipopolysaccharide‐induced inflammatory cytokine levels in murine macrophages. Additionally, our results provided a preclinical rationale in imiquimod (IMQ)‐induced BALB/c mouse model, where niclosamide diligently mitigated the IMQ‐induced epidermal hyperplasia and inflammation by downregulating STAT3, p65 NF‐κB, and NFATc‐1 transcription factors along with Akt, Ki‐67, and ICAM‐1 protein expression.

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Section: Discussionsupporting

confidence: 91%

Repurposing an old drug for new use: Niclosamide in psoriasis‐like skin inflammation

Thatikonda

Pooladanda

Godugu

2019

Journal Cellular Physiology

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“…Papaccio et al [28] reported overexpression of adhesion molecules, namely, increased ICAM-1 mRNA in islets, in FK506-treated mice. This finding suggests that FK506 could upregulate expression of adhesion molecules in several tissues.…”

Section: Discussionmentioning

confidence: 99%

Tacrolimus Induces Glomerular Injury via Endothelial Dysfunction Caused by Reactive Oxygen Species and Inflammatory Change

Kidokoro¹,

Satoh²,

Nagasu³

et al. 2012

Kidney Blood Press Res

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Background/Aims: The immunosuppressive drug tacrolimus (FK506) is used clinically to reduce the rejection rate in patients with kidney transplantation; however, the resultant nephrotoxicity remains a serious problem. In the present study we attempted to elucidate the mechanisms of glomerular injury induced by FK506 and the renoprotective effects of the angiotensin II receptor blocker telmisartan. Methods: Seven-week-old male Wistar rats were divided into three groups: vehicle group, FK506 group, and FK506 + telmisartan group. After 8 weeks, we assessed kidney function and renal morphological changes including oxidative stress. We also assessed the effect of FK506 in human glomerular endothelial cells (hGECs) with regard to reactive oxygen species (ROS). Results: FK506 induced ROS production via activation of NAD(P)H oxidase in the glomeruli. Expression of ICAM mRNA was increased in glomeruli from the FK506 group. These effects resulted in macrophage infiltration into the glomeruli. FK506 directly promoted NAD(P)H oxidase activity and accelerated production of ROS in hGECs. Conversely, cotreatment with telmisartan inhibited both NAD(P)H oxidase activity and production of ROS. Conclusion: These findings suggest that glomerular injury resulting from FK506 is caused by oxidative stress mediated by activation of NAD(P)H oxidase and that telmisartan exerts a renoprotective effect via antioxidative activity.

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Decrease of CD4+CD25highFoxp3+ regulatory T cells and elevation of CD19+BAFF-R+ B cells and soluble ICAM-1 in myasthenia gravis

Xiao

et al. 2008

Clinical Immunology

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Tacrolimus, but not Cyclosporine A, significantly increases expression of ICAM-1 and IFN-? in the NOD mouse

Cited by 5 publications

References 26 publications

Repurposing an old drug for new use: Niclosamide in psoriasis‐like skin inflammation

Repurposing an old drug for new use: Niclosamide in psoriasis‐like skin inflammation

Tacrolimus Induces Glomerular Injury via Endothelial Dysfunction Caused by Reactive Oxygen Species and Inflammatory Change

Decrease of CD4+CD25highFoxp3+ regulatory T cells and elevation of CD19+BAFF-R+ B cells and soluble ICAM-1 in myasthenia gravis

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