Melatonin reduces airway inflammation in ovalbumin-induced asthma

Shin, In‐Sik; Park, Ji Won; Shin, Na‐Rae; Jeon, Chan‐Mi; Kwon, Ok‐Kyoung; Kim, Joong Sun; Kim, Jong-Choon; Oh, Sei‐Ryang; Ahn, Ki Hoon

doi:10.1016/j.imbio.2014.08.004

Cited by 54 publications

(47 citation statements)

References 34 publications

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“…Our results showed an efficient induction of bronchial asthma evidenced by significant and massive reductions in the respiratory functions TV and PEFR (table 1), which agreed with previous investigations in rats and mice [35,36,37]. Cytokines, particularly TNF-α, are involved in the initiation and progression of airway inflammation [38,39], with IL-5 particularly reported to have a central role in the initiation of eosinophilic airway inflammation [40], strongly agreeing with our results (table 2). IgE plays a key role in the pathogenesis of extrinsic asthma, as in our model (table 3), through stimulating mast cell degranulation [41].…”

Section: Discussionsupporting

confidence: 91%

Assessment of the Mechanistic Role of Cinnarizine in Modulating Experimentally-Induced Bronchial Asthma in Rats

2015

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Background/Aims: Calcium influx, inflammatory infiltration, cytokine production, immunoglobulin E activation and oxidative stress play coordinated roles in bronchial asthma pathogenesis. We aim to assess the protective effect of cinnarizine against experimentally induced bronchial asthma. Methods: Bronchial asthma was induced by ovalbumin sensitization and challenge. Rats were allocated into a normal control, an asthma control, a dexamethasone (standard) treatment, and 2 cinnarizine treatment groups. The respiratory functions tidal volume (TV) and peak expiratory flow rate (PEFR), the inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-5 (IL-5) in lung tissue, the allergic immunoglobulin IgE in serum, the absolute eosinophil count (AEC) in bronchoalveolar lavage fluid (BALF), as well as the oxidative and nitrosative markers glutathione reduced (GSH) and superoxide dismutase (SOD) in lung tissue and nitric oxide end products (NOx) in BALF were assessed, followed by a histopathological study. Results: Cinnarizine administration significantly restored TV, PEFR, TNF-α, IL-5, IgE, AEC, GSH, SOD and NOx values back to normal levels, and significantly decreased perivascular and peribronchiolar inflammatory scores. Conclusion: Cinnarizine may protect against experimental bronchial asthma. Suppressant effect of cinnarizine on pro-inflammatory cytokines release, IgE antibody production, eosinophil infiltration as well as oxidative and nitrosative stress may explain its anti-asthmatic potential.

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Section: Discussionsupporting

confidence: 91%

Assessment of the Mechanistic Role of Cinnarizine in Modulating Experimentally-Induced Bronchial Asthma in Rats

2015

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“…A question that arises from our study is how TLR9 regulated allergic airway inflammation. Exogenous melatonin has been reported to inhibit the asthmatic responses in a murine model of OVA‐induced allergic asthma . Whether endogenous melatonin has the same protective effect and was regulated by TLR9 is still unknown.…”

Section: Resultsmentioning

confidence: 99%

JNK–TLR9 signal pathway mediates allergic airway inflammation through suppressing melatonin biosynthesis

Shen

Fang

et al. 2016

Journal of Pineal Research

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Toll-like receptors (TLRs) play pivotal role in the pathogenesis of allergic airway diseases such as asthma. TLR9 is one of the most extensively studied TLRs as an approach to treat asthma. In this study, we investigated the role of TLR9 in the allergic airway inflammation and the underlying mechanism. Wild-type (WT) mice and TLR9(-/-) mice were sensitized and challenged with OVA to establish allergic airway disease model. We found that the expression of TLR9 was elevated concomitantly with airway inflammation post-OVA challenge, and TLR9 deficiency effectively inhibited airway inflammation, including serum OVA-specific immunoglobulin E (IgE), pulmonary inflammatory cell recruitment, mucus secretion, and bronchoalveolar lavage fluid (BALF) inflammatory cytokine production. Meanwhile, the protein expression of hydroxyindole-o-methyltransferase (HIOMT) in lung tissues, the level of melatonin in serum, and BALF were reduced in OVA-challenged WT mice, while these reductions were significantly restored by TLR9 deficiency. Additionally, we showed that although TLR9 deficiency had no effect on OVA-induced phosphorylation of JNK, inhibition of JNK by specific inhibitor SP600125 significantly decreased OVA-induced expression of TLR9, suggesting that JNK is the upstream signal molecular of TLR9. Furthermore, SP600125 treatment promoted resolution of allergic airway inflammation in OVA-challenged WT mice, but not further ameliorated allergic airway inflammation in OVA-challenged TLR9(-/-) mice. Similarly, SP600125 significantly restored the protein expression of HIOMT and the level of melatonin in OVA-challenged WT mice, while such effect was not further enhanced by TLR9 deficiency. Collectively, our results indicated that JNK-TLR9 signal pathway mediates allergic airway inflammation through suppressing melatonin biosynthesis.

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“…The clear example of antioxidant therapy to the soot or CB caused injury came from the effect of artesunate, which significantly decreased the levels of oxidative biomarkers, 3-nitrotyrosine, 8-isoprostane, and 8-OHdG in a mice model of lung injury (259). Similarly, melatonin, a natural antioxidant, was found to reduce airway inflammation in an asthma model (260). Recently, mitochondrial-based antioxidant therapy downregulates TGF-β-mediated deposition of collagen in a murine model of asthma (261).…”

Section: Possible Therapeutic Interventions To Combat Soot- or Cb-assmentioning

confidence: 99%

The Toxicological Mechanisms of Environmental Soot (Black Carbon) and Carbon Black: Focus on Oxidative Stress and Inflammatory Pathways

2017

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The environmental soot and carbon blacks (CBs) cause many diseases in humans, but their underlying mechanisms of toxicity are still poorly understood. Both are formed after the incomplete combustion of hydrocarbons but differ in their constituents and percent carbon contents. For the first time, “Sir Percival Pott” described soot as a carcinogen, which was subsequently confirmed by many others. The existing data suggest three main types of diseases due to soot and CB exposures: cancer, respiratory diseases, and cardiovascular dysfunctions. Experimental models revealed the involvement of oxidative stress, DNA methylation, formation of DNA adducts, and Aryl hydrocarbon receptor activation as the key mechanisms of soot- and CB-induced cancers. Metals including Si, Fe, Mn, Ti, and Co in soot also contribute in the reactive oxygen species (ROS)-mediated DNA damage. Mechanistically, ROS-induced DNA damage is further enhanced by eosinophils and neutrophils via halide (Cl− and Br−) dependent DNA adducts formation. The activation of pulmonary dendritic cells, T helper type 2 cells, and mast cells is crucial mediators in the pathology of soot- or CB-induced respiratory disease. Polyunsaturated fatty acids (PUFAs) were also found to modulate T cells functions in respiratory diseases. Particularly, telomerase reverse transcriptase was found to play the critical role in soot- and CB-induced cardiovascular dysfunctions. In this review, we propose integrated mechanisms of soot- and CB-induced toxicity emphasizing the role of inflammatory mediators and oxidative stress. We also suggest use of antioxidants and PUFAs as protective strategies against soot- and CB-induced disorders.

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Melatonin reduces airway inflammation in ovalbumin-induced asthma

Cited by 54 publications

References 34 publications

Assessment of the Mechanistic Role of Cinnarizine in Modulating Experimentally-Induced Bronchial Asthma in Rats

Assessment of the Mechanistic Role of Cinnarizine in Modulating Experimentally-Induced Bronchial Asthma in Rats

JNK–TLR9 signal pathway mediates allergic airway inflammation through suppressing melatonin biosynthesis

The Toxicological Mechanisms of Environmental Soot (Black Carbon) and Carbon Black: Focus on Oxidative Stress and Inflammatory Pathways

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