Mediator Archives - World Asthma Foundation

Persistent nasal symptoms and mediator release after continuous pollen exposure in an environmental challenge chamber.

Ann Allergy Asthma Immunol. 2016 Jun 1;

Authors: Okuma Y, Okamoto Y, Yonekura S, Iinuma T, Sakurai T, Hamasaki S, Ohki Y, Yamamoto H, Sakurai D

Abstract
BACKGROUND: Immediate- and late-phase reactions are associated with nasal symptoms of patients with allergic rhinitis.
OBJECTIVE: To examine the symptoms and mediators released after continuous allergen exposure in an environmental challenge chamber (ECC).
METHODS: Fifteen patients with Japanese cedar pollinosis were enrolled in this study and continuously exposed to cedar pollen at a concentration of 8,000 grains/m(3) for 3 hours in an ECC. Nasal function tests were performed, and nasal secretions were collected before pollen exposure (0 hour), immediately after exiting the ECC (3 hours), and 6 hours after exiting the ECC (9 hours). Symptom scores were recorded every 30 minutes in the ECC and every 3 hours after exiting the ECC. The frequency of sneezing and nose blowing also was monitored.
RESULTS: The severity of symptoms in the ECC peaked approximately 2 hours after the beginning of pollen exposure and continued more than 6 hours after leaving the ECC. Concentrations of histamine, tryptase, interleukins 5, 3, 33, and 31, and substance P increased over time, whereas that of nasal fractional exhaled nitric oxide decreased.
CONCLUSION: Various mediators are released during continuous allergen exposure, which subsequently induce persistent nasal symptoms. Effective treatment is required to control the intense inflammation observed after allergen exposure.

PMID: 27263086 [PubMed – as supplied by publisher]

View full post on pubmed: asthma

Exchange Protein Directly Activated by cAMP (epac): A Multidomain cAMP Mediator in the Regulation of Diverse Biological Functions.

Pharmacol Rev. 2013;65(2):670-709

Authors: Schmidt M, Dekker FJ, Maarsingh H

Abstract
Since the discovery nearly 60 years ago, cAMP is envisioned as one of the most universal and versatile second messengers. The tremendous feature of cAMP to tightly control highly diverse physiologic processes, including calcium homeostasis, metabolism, secretion, muscle contraction, cell fate, and gene transcription, is reflected by the award of five Nobel prizes. The discovery of Epac (exchange protein directly activated by cAMP) has ignited a new surge of cAMP-related research and has depicted novel cAMP properties independent of protein kinase A and cyclic nucleotide-gated channels. The multidomain architecture of Epac determines its activity state and allows cell-type specific protein-protein and protein-lipid interactions that control fine-tuning of pivotal biologic responses through the “old” second messenger cAMP. Compartmentalization of cAMP in space and time, maintained by A-kinase anchoring proteins, phosphodiesterases, and ?-arrestins, contributes to the Epac signalosome of small GTPases, phospholipases, mitogen- and lipid-activated kinases, and transcription factors. These novel cAMP sensors seem to implement certain unexpected signaling properties of cAMP and thereby to permit delicate adaptations of biologic responses. Agonists and antagonists selective for Epac are developed and will support further studies on the biologic net outcome of the activation of Epac. This will increase our current knowledge on the pathophysiology of devastating diseases, such as diabetes, cognitive impairment, renal and heart failure, (pulmonary) hypertension, asthma, and chronic obstructive pulmonary disease. Further insights into the cAMP dynamics executed by the Epac signalosome will help to optimize the pharmacological treatment of these diseases.

PMID: 23447132 [PubMed – as supplied by publisher]

View full post on pubmed: asthma