Novel drug targets for asthma and COPD: Lessons learned from in vitro and in vivo models

Baker, Katie; Bonvini, Sara J.; Donovan, Chantal; Foong, Rachel E.; Han, Bing; Jha, Aruni; Shaifta, Yasin; Smit, Marieke; Johnson, Jill; Moir, Lyn M.

doi:10.1016/j.pupt.2014.05.008

Cited by 29 publications

(24 citation statements)

References 266 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Human lung exposure to deleterious effects of metal can result to pulmonary fibrosis . Moreover, long‐term inflammation of the lung by metals destroyed the alveolar walls .…”

Section: Introductionmentioning

confidence: 99%

Barium chloride dose‐dependently induced heart and lung injury in Wistar rats

Omole

Alabi

Aturamu³

et al. 2019

Environmental Toxicology

View full text Add to dashboard Cite

Barium (Ba) is one of the environmental pollutant metals that incite deleterious effects on human health. The present study investigated the effects of exposure to different doses of barium chloride (BaCl2) on heart and lung of Wistar rats. Rats were exposed to BaCl2 at 150, 300, and 600 mg/L for seven consecutive days. Results indicated that exposure to Ba caused heart and lung damage evidenced by significant increase in plasma lactate dehydrogenase and creatine kinase activities, total cholesterol, triglyceride, and low‐density lipoprotein‐cholesterol levels, while high‐density lipoprotein‐cholesterol level decreased when compared with control. Moreover, BaCl2 significantly decreased superoxide dismutase, catalase, and acetylcholinesterase activities as well as glutathione level in heart and lung of the treated rats. Furthermore, the dose‐dependent increase in cardiac and lung lipid peroxidation, advanced oxidative protein product and nitric oxide levels were accompanied by marked increase in metallothionein in the BaCl2‐treated rats. Administration of BaCl2 altered hematological parameters and significantly increased concentrations of interleukin‐6 in the treated rats. Histology analysis showed significant alteration in the heart and lung tissues of Ba‐treated rats. In conclusion, BaCl2‐induced heart and lung damages via disruption of antioxidant defense systems, and activation of inflammatory mediators and alteration in hematological parameters in rats.

show abstract

“…Human lung exposure to deleterious effects of metal can result to pulmonary fibrosis . Moreover, long‐term inflammation of the lung by metals destroyed the alveolar walls .…”

Section: Introductionmentioning

confidence: 99%

Barium chloride dose‐dependently induced heart and lung injury in Wistar rats

Omole

Alabi

Aturamu³

et al. 2019

Environmental Toxicology

View full text Add to dashboard Cite

show abstract

“…Members of the TRP channel family have been implicated in a number of critical phagocytic functions, including particle uptake, migration, and reactive oxygen species (ROS) production (5,(8)(9)(10)(11). Numerous studies (12)(13)(14)(15) have suggested TRP channels as potential targets for the development of therapies in pulmonary inflammation because of their abundant and diverse cellular expression throughout the respiratory tree. Although TRPC6 channels have been previously identified in lung macrophages and shown to be up-regulated in COPD, their precise role in the pathophysiology of the disease is yet to be determined (16).…”

mentioning

confidence: 99%

TRPC6 channel translocation into phagosomal membrane augments phagosomal function

Riazanski

Gabdoulkhakova

Boynton

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Defects in the innate immune system in the lung with attendant bacterial infections contribute to lung tissue damage, respiratory insufficiency, and ultimately death in the pathogenesis of cystic fibrosis (CF). Professional phagocytes, including alveolar macrophages (AMs), have specialized pathways that ensure efficient killing of pathogens in phagosomes. Phagosomal acidification facilitates the optimal functioning of degradative enzymes, ultimately contributing to bacterial killing. Generation of low organellar pH is primarily driven by the V-ATPases, proton pumps that use cytoplasmic ATP to load H+ into the organelle. Critical to phagosomal acidification are various channels derived from the plasma membrane, including the anion channel cystic fibrosis transmembrane conductance regulator, which shunt the transmembrane potential generated by movement of protons. Here we show that the transient receptor potential canonical-6 (TRPC6) calcium-permeable channel in the AM also functions to shunt the transmembrane potential generated by proton pumping and is capable of restoring microbicidal function to compromised AMs in CF and enhancement of function in non-CF cells. TRPC6 channel activity is enhanced via translocation to the cell surface (and then ultimately to the phagosome during phagocytosis) in response to G-protein signaling activated by the small molecule (R)-roscovitine and its derivatives. These data show that enhancing vesicular insertion of the TRPC6 channel to the plasma membrane may represent a general mechanism for restoring phagosome activity in conditions, where it is lost or impaired.

show abstract

“…Clinically, COPD are not easily treated with currently available drugs that include antitussives, cholinergics, bronchodilators, and anti‐inflammatory steroids (Jeffery, ). Even treatments with recently developed anti‐cytokine agents, leukotriene receptor antagonist, and phosphodiesterase 4 inhibitor can only provide limited success (Baker et al, ). Because the etiology and progress of COPD are complex, pinpointing the appropriate molecular target(s) that can obviate symptoms and progress of COPD has been challenging (Barnes, ).…”

Section: Introductionmentioning

confidence: 99%

Aurantio‐obtusin, an anthraquinone from cassiae semen, ameliorates lung inflammatory responses

Park

Lim

et al. 2018

Phytotherapy Research

View full text Add to dashboard Cite

The purpose of the present study is to find the natural compound(s) having a therapeutic potential to treat lung inflammatory disorders. In our screening procedure, the methanol extract of the seeds of Cassia obtusifolia (cassiae semen) inhibited inducible nitric oxide synthase-catalyzed nitric oxide production in alveolar macrophages (MH-S). From the extract, 8 major anthraquinone derivatives were successfully isolated. They are chrysophanol, physcion, 2-hydroxy-emodin 1-methyl ether, obtusifolin, obtusin, aurantio-obtusin, chryso-obtusin, and gluco-obtusifolin, among which aurantio-obtusin (IC = 71.7 μM) showed significant inhibitory action on nitric oxide production from lipopolysaccharide-treated MH-S cells, mainly by downregulation of inducible nitric oxide synthase expression. This down-regulatory action of aurantio-obtusin was mediated at least in part via interrupting c-Jun N-terminal kinase/IκB kinase/nuclear transcription factor-κB pathways. Aurantio-obtusin also inhibited IL-6 production in IL-1β-treated lung epithelial cells, A549. Importantly, this compound (10 and 100 mg/kg) by oral administration attenuated lung inflammatory responses in a mouse model of lipopolysaccharide-induced acute lung injury. Therefore, it is for the first time found that aurantio-obtusin may have a therapeutic potential for treating lung inflammatory diseases.

show abstract

Novel drug targets for asthma and COPD: Lessons learned from in vitro and in vivo models

Cited by 29 publications

References 266 publications

Barium chloride dose‐dependently induced heart and lung injury in Wistar rats

Barium chloride dose‐dependently induced heart and lung injury in Wistar rats

TRPC6 channel translocation into phagosomal membrane augments phagosomal function

Aurantio‐obtusin, an anthraquinone from cassiae semen, ameliorates lung inflammatory responses

Contact Info

Product

Resources

About