Non-antibiotic properties of tetracyclines as anti-allergy and asthma drugs

Joks, Rauno; Durkin, Helen G.

doi:10.1016/j.phrs.2011.04.001

Cited by 27 publications

(15 citation statements)

References 40 publications

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“…5a). Our results are consistent with previous studies where tetracycline treatment induced IL-2 release (29). To the best of our knowledge, no previous studies investigated the release of IL-17 and IL-2 from splenocytes.…”

Section: Effect Of Tgc On Il-17 and Il-2 Release In Con A Pretreated supporting

confidence: 93%

Immunomodulatory Effects of Tigecycline in Balb/C Mice

Elhayek

Fararjeh²,

Assaf

et al. 2018

Acta Pharmaceutica

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Tigecycline is a glycylcycline antibiotic approved by the FDA for the treatment of complicated infections. Despite its effectiveness, the FDA announced a warning of increasing mortality associated with its use. There is, however, no clear explanation for this side effect. Previous reports found a possible effect of tigecycline on leukocyte proliferation and proinflammatory cytokine release. We t herefore i nvestigated the effect of tigecycline on the immune components and response in Balb/c mice in vivo and in vitro. It was found that tigecycline enhanced lymphocyte proliferation and significantly increased cellular infiltration within the footpad, as based on DTH testing, but reduced the hemagglutination titer. In splenocyte cultures, tigecycline suppressed splenocyte proliferation with IC50 3-5 mmol L-1, significantly increased IL-2 secretion and reduced IL-17 secretion in a dose dependent mode. In conclusion, tigecycline is safe at therapeutic and sub-therapeutic doses, but it could still have an immunomodulatory effect at higher doses. Use of higher doses of tigecycline requires further investigation.

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Section: Effect Of Tgc On Il-17 and Il-2 Release In Con A Pretreated supporting

confidence: 93%

Immunomodulatory Effects of Tigecycline in Balb/C Mice

Elhayek

Fararjeh²,

Assaf

et al. 2018

Acta Pharmaceutica

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“…8). Interest in this drug stems from its modulatory effects against a number of inflammatory conditions both in human subjects and animal models (8).…”

Section: Discussionmentioning

confidence: 99%

“…Joks and Durkin (reviewed in Ref. 8), in a pioneering study, showed that minocycline harbors oral steroid-sparing properties in a cohort of human subjects with both moderate persistent and severe persistent asthma (5). Minocycline was shown to be efficacious in reducing IgE production in an in vitro system as well as in response to BPO(14)-KLH (6,42).…”

Section: Discussionmentioning

confidence: 99%

“…The role of p38 MAPK is increasingly being recognized in a number of aspects of allergic responses, and the kinase is becoming a viable therapeutic target for the treatment of asthma symptoms (45). Minocycline was suggested to reduce the number of CD4 ϩ and CD8 ϩ T cells but not B cells or monocytes from asthmatic individuals who display p38 MAPK phosphorylation, as assessed by FACS analysis, suggesting a mechanistic link between the function of the drug and IgE suppression (8). In our experimental model and using direct CD4 ϩ T cells stimulation, minocycline exerted no effect on TCR-mediated p38 MAPK, suggesting, perhaps, that the effect observed in asthmatic individuals may not be associated with TCR stimulation or is the result of an indirect effect.…”

Section: Discussionmentioning

confidence: 99%

“…Minocycline has been suggested to block several signal transduction pathways that are critical for the expression of inflammatory genes (7,8).…”

mentioning

confidence: 99%

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Minocycline Blocks Asthma-associated Inflammation in Part by Interfering with the T Cell Receptor-Nuclear Factor κB-GATA-3-IL-4 Axis without a Prominent Effect on Poly(ADP-ribose) Polymerase

Naura

Kim

et al. 2013

Journal of Biological Chemistry

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Background: Minocycline protects against asthma independently of its antibiotic function. Results: Minocycline blocks asthma-associated traits, including IgE production, by modulating the TCR-NF-B-GATA-3-IL-4 axis but not the TCR/NFAT1/IL-2 pathway without a direct effect on PARP activity. Conclusion: These results provide new insight into the mechanism of action of minocycline. Significance: These results provide further support to the therapeutic potential of minocycline in reducing or preventing allergen-induced asthma symptoms.

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The anti‐anaphylactoid effects of Piperine through regulating MAS‐related G protein‐coupled receptor X2 activation

Qiao

Che

et al. 2020

Phytotherapy Research

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Mast cells play an important role in inflammatory and allergic diseases. MAS-related G protein-coupled receptor X2 (MRGPRX2) is a novel G protein-coupled receptor in mast cells that mediates drug-induced anaphylactoid reactions. Piperine has been reported to have anti-inflammatory and anti-allergic pharmacological activities. However, whether the pharmacological effects are regulated by MRGPRX2 has not yet been reported. The purpose of this study was to assess the anti-anaphylactoid effect of Piperine and to explore its potential mechanism. The anti-anaphylactoid effect of Piperine was assessed by an in vivo mouse hindpaw extravasation model. Mast cell intracellular calcium mobilization was measured by a calcium imaging assay. An enzyme immunoassay was used to evaluate the release of pro-inflammatory factors from stimulated mast cells. Activated mast cell related signals were assessed by western blot. A cell membrane chromatography assay was used to determine the binding characteristics of Piperine and MRGPRX2. The results showed that Piperine suppressed mast cell intracellular Ca 2+ mobilization, inhibited cytokines and chemokines release, and down-regulated the phosphorylation level of phospholipase Cγ1, protein kinase C, inositol 1,4,5-triphate receptor, P38, protein kinase B, and ERK. Meanwhile, Piperine can bind to MRGPRX2 as a specific antagonist. Hence, Piperine can be served as a novel therapeutic drug candidate for MRGPRX2-mediated anaphylactoid reactions. K E Y W O R D Santianaphylactoid effects, Ca 2+ influx, mast cells, MRGPRX2, Piperine

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Non-antibiotic properties of tetracyclines as anti-allergy and asthma drugs

Cited by 27 publications

References 40 publications

Immunomodulatory Effects of Tigecycline in Balb/C Mice

Immunomodulatory Effects of Tigecycline in Balb/C Mice

Minocycline Blocks Asthma-associated Inflammation in Part by Interfering with the T Cell Receptor-Nuclear Factor κB-GATA-3-IL-4 Axis without a Prominent Effect on Poly(ADP-ribose) Polymerase

The anti‐anaphylactoid effects of Piperine through regulating MAS‐related G protein‐coupled receptor X2 activation

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