metallothionein and Asthma

Topics: Adrenal Cortex Hormones; Animals; Anti-Inflammatory Agents; Arthritis; Asthma; Cytokines; Extracellular Matrix; Fever; Heat-Shock Proteins; Humans; Inflammation; Leukotrienes; Metallothionein; Phagocytosis; Platelet Activating Factor; Prostaglandins

Acupuncture has long been used for asthma treatment but the underlying mechanism remains unclear. Previous study showed that metallothionein-2 (MT-2) was significantly decreased in asthmatic lung tissue. However, the relationship between acupuncture treatment and MT-2 expression during asthma is still unknown, and the detailed effect analysis of MT-2 on phosphorylation in airway smooth muscle cells (ASMCs) is also unclear.. The acupuncture effect on pulmonary resistance (RL) was investigated in a rat model of asthma, and the mRNA and protein levels of MT-2 in lung tissue were detected. Primary ASMCs were isolated and treated with MT-2 recombinant protein to study the MT-2 effects on ASMC relaxation. A Phospho Explorer antibody microarray was applied to detect protein phosphorylation changes associated with MT-2-induced ASMC relaxation. Bioinformatic analysis were performed with PANTHER database, DAVID and STRING. Phosphorylation changes in key proteins were confirmed by Western blot.. Acupuncture significantly reduced RL at 2-5 min (P < 0.05 vs asthma) in asthmatic rats. Acupuncture continued to increase MT-2 mRNA expression in lung tissue for up to 14 days (P < 0.05 vs asthma). The MT-2 protein expression was significantly decreased in the asthmatic rats (P < 0.05 vs control), while MT-2 protein expression was significantly increased in the asthmatic model group treated with acupuncture (P < 0.05 vs asthma). Primary ASMCs were successfully isolated and recombinant MT-2 protein (100, 200, 400 ng/ml) significantly relaxed ASMCs (P < 0.05 vs control). MT-2 induced phosphorylation changes in 51 proteins. Phosphorylation of 14 proteins were upregulated while 37 proteins were downregulated. PANTHER classification revealed eleven functional groups, and the phosphorylated proteins were identified as transferases (27.8 %), calcium-binding proteins (11.1 %), etc. DAVID functional classification showed that the phosphorylated proteins could be attributed to eight functions, including protein phosphorylation and regulation of GTPase activity. STRING protein-protein interaction network analysis showed that Akt1 was one of the most important hubs for the phosphorylated proteins. The phosphorylation changes of Akt1 and CaMK2β were consistent in both the Phospho Explorer antibody microarray and Western blot.. Acupuncture can significantly ameliorate RL, and the MT-2 mRNA and protein levels in lung tissue are increased during treatment. MT-2 significantly relaxes ASMCs and induces a series of protein phosphorylation. These phosphorylation changes, including Akt1 and CaMK2β, may play important roles in the therapeutic effects of acupuncture on asthma.

Topics: Acupuncture Therapy; Animals; Asthma; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Lung; Male; Metallothionein; Muscle Relaxation; Myocytes, Smooth Muscle; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; RNA, Messenger; Vascular Resistance

Complex interaction between anthropogenic activities, air quality and human health in urban areas, such as in Cracow sustains the need for the development of an interdisciplinary and integrated risk-assessment methodology. In such purpose, we propose a pilot study performed on asthmatics and based on a combined use of a biomarker, such as metallothionein 2A (MT-2A) in the characterization of human exposure to one or a mixture of pollutants and of Geographical Information Systems (G.I.S.) which integrates climatic and urban anthropogenic parameters in the assessment of spatio-temporal dispersion of air pollutants. Considering global incidence of air pollution on asthma and on peripheral blood lymphocytes MT-2A expression should provide a complementary information on biological risks linked to urban anthropogenic activities. Such study would help for the establishment of a sustainable development in urban areas that can maintain the integrity of air quality and preserve human health.

Topics: Air Movements; Air Pollution; Asthma; Biomarkers; Cities; Environmental Exposure; Environmental Monitoring; Geographic Information Systems; Humans; Metallothionein; Poland; Risk Assessment; Urban Health