This review focuses on the role and regulation of mucin glycoproteins (mucins) in airway health and disease. Mucins are highly glycosylated macromolecules (≥50% carbohydrate, wt/wt). MUC protein ba...

Respiratory Tract Mucin Genes and Mucin Glycoproteins in Health and Disease

Oligosaccharide specificity of galectins: a search by frontal affinity chromatography.

https://apam.columbia.edu/files/seasdepts/applied-physics-and-applied-math/pdf-files/06-salk-chan.pdf

Cerium and yttrium oxide nanoparticles are neuroprotective.

The concept of a purinergic signaling system, using purine nucleotides and nucleosides as extracellular messengers, was first proposed over 30 years ago. After a brief introduction and update of purinoceptor subtypes, this article focuses on the diverse pathophysiological roles of purines and pyrimidines as signaling molecules. These molecules mediate short-term (acute) signaling functions in neurotransmission, mechanosensory transduction, secretion and vasodilatation, and long-term (chronic) signaling functions in cell proliferation, differentiation, and death involved in development and regeneration. Plasticity of purinoceptor expression in pathological conditions is frequently observed, including an increase in the purinergic component of autonomic cotransmission. Recent advances in therapies using purinergic-related drugs in a wide range of pathological conditions will be addressed with speculation on future developments in the field.

/pdf/pathophysiology-and-therapeutic-potential-of-purinergic-5eb03t8gkw.pdf

Pathophysiology and Therapeutic Potential of Purinergic Signaling

Summary: Macrolides have diverse biological activities and an ability to modulate inflammation and immunity in eukaryotes without affecting homeostatic immunity. These properties have led to their long-term use in treating neutrophil-dominated inflammation in diffuse panbronchiolitis, bronchiectasis, rhinosinusitis, and cystic fibrosis. These immunomodulatory activities appear to be polymodal, but evidence suggests that many of these effects are due to inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and nuclear factor kappa B (NF-κB) activation. Macrolides accumulate within cells, suggesting that they may associate with receptors or carriers responsible for the regulation of cell cycle and immunity. A concern is that long-term use of macrolides increases the emergence of antimicrobial resistance. Nonantimicrobial macrolides are now in development as potential immunomodulatory therapies.

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

Tobacco Smoke Control of Mucin Production in Lung Cells Requires Oxygen Radicals AP-1 and JNK

Fungal galectins, sequence and specificity of two isolectins from Coprinus cinereus.

Bacterial flagellin can interact with both Toll-like receptor 5 (TLR5) and the cell surface glycolipid, asialoGM1, to activate an innate immune response. The induction of mucin by flagellin in human lung epithelial cells (NCIH292) is dependent on asialoGM1 ligation, ATP receptor signaling, Ca2+ mobilization, and Erk1/2 activation. Conversely, the activation of NF-kappaB by flagellin is dependent on signaling through TLR5. These results prompted us to ask whether the flagellin-induced TLR5 signaling pathway was intersecting with or mutually independent of the nucleotide receptor pathway activated downstream of asialoGM1. Herein, we demonstrate that the release of ATP induced by flagellin is dependent on a Toll signaling cascade. Although Toll was able to activate NF-kappaB in the absence of extracellular ATP, Toll required ATP to activate Erk1/2. These results suggest interdependence between the asialoGM1 and TLR5 pathways and reveal a previously unsuspected role for autocrine extracellular ATP signaling in TLR signaling.

/pdf/asialogm1-and-tlr5-cooperate-in-flagellin-induced-nucleotide-4hcz83hcsn.pdf

AsialoGM1 and TLR5 Cooperate in Flagellin-Induced Nucleotide Signaling to Activate Erk1/2

SPECIFIC AIMSMucus hypersecretion is an important clinical feature of asthma. While the etiology is not well understood, hypersecretion has been linked to the presence of cytokines such as IL-4, IL-5, IL-9, and IL-13 in the inflamed airway. Recent work has shown that IL-13-associated events in the asthmatic airway of IL-13 transgenic mice are dependent on adenosine accumulation and altered expression of adenosine receptors. Although the abundant adenosine present in asthmatic airways has been recognized for its contributions to airway hyperreactivity and inflammation, no studies have yet implicated adenosine in mucus hypersecretion. In this study, we examined the possibility that adenosine contributes to asthmatic mucus hypersecretion.PRINCIPAL FINDINGS1. Ligation of an adenosine receptor stimulates MUC2 gene expressionAlthough most asthma models focus on the mucin gene MUC5AC, we focus here on the mucin gene MUC2. Recent work has shown that MUC2 is up-regulated in asthmatic airways. Due to the relative i...

https://faseb.onlinelibrary.wiley.com/doi/pdf/10.1096/fj.04-1964fje

Adenosine up-regulation of the mucin gene, MUC2, in asthma.

https://escholarship.org/content/qt8pf8r7vs/qt8pf8r7vs.pdf?t=lnrzrv

Anatol Sucher

Papers

Tobacco Smoke Control of Mucin Production in Lung Cells Requires Oxygen Radicals AP-1 and JNK

Fungal galectins, sequence and specificity of two isolectins from Coprinus cinereus.

AsialoGM1 and TLR5 Cooperate in Flagellin-Induced Nucleotide Signaling to Activate Erk1/2

Adenosine up-regulation of the mucin gene, MUC2, in asthma.

Viral Regulation of the Long Distance Axonal Transport of Herpes Simplex Virus Nucleocapsid