Modulation of airway inflammation and resistance in mice by a nicotinic receptor agonist

Abstract

Nicotinic agonists, including 1,1-dimethyl-4-phenylpiperazinium (DMPP), have antiinflammatory properties and in some instances smooth muscle relaxing effects. Since inflammation and airway smooth muscle contraction are two major components of asthma, the present authors investigated the effects of DMPP on airway inflammation and airway resistance in a mouse model of asthma.Mice were sensitised and challenged with ovalbumin (OVA) and treated either intraperitoneally or intranasally with DMPP. The effect of DMPP was tested on airway inflammation, airway resistance and on the increase of intracellular calcium in bronchial smooth muscle cells.DMPP given either during sensitisation, OVA challenges or throughout the protocol prevented lung inflammation and decreased the serum level of OVA specific immunoglobulin E. DMPP administration reduced the number of total cells, lymphocytes and eosinophils in the bronchoalveolar lavage (BAL) fluid. Intranasal DMPP administration was as effective as dexamethasone (DEXA) in reducing total cell count and eosinophil counts in BAL fluid. DMPP, but not DEXA, reduced tissue inflammation. Intranasal DMPP, given 10 min before the test, reduced airway responsiveness to metacholine. DMPP also reduced the increase in intracellular calcium in response to bradykinin.In conclusion, these results show that 1,1-dimethyl-4-phenylpiperazinium reduces lung inflammation and prevents airway hyperresponsiveness in the mouse model of asthma.

Diaphragm Muscle Contraction Decrease in a Mouse Model of Ovalbumin-Induced Allergic Airway Inflammation

“…There were previously reported that OVA increased the breathing resistance of the mice [11], resistive breathing induced IL-4 expression in diaphragm muscle [12], Th2 cytokines such as IL-4 and IL-13 induce iNOS expression through the STAT-6 pathway [13][14][15][16][17], iNOS reduced diaphragm muscle contraction, inhibition of iNOS induction and inhibition of NOS activity prevented diaphragm muscle contractile dysfunction [18]. Study results of ours are in agreement with study that previously reported.…”

CD34 Is Required for Dendritic Cell Trafficking and Pathology in Murine Hypersensitivity Pneumonitis

“…The reduced pulmonary inflammation in Cd34 2/2 mice was further confirmed via analysis of hematoxylin and eosinstained lung sections (Figure 2), using a well-described method of lung histology analysis (3,15,25,26). Briefly, slides were evaluated for the level of peribronchial, perivascular, and parenchymal (tissue and alveoli) infiltration (see METH-ODS).…”

Dimethyphenylpiperazinium, a nicotinic receptor agonist, downregulates inflammation in monocytes/macrophages through PI3K and PLC chronic activation

“…Studies have demonstrated that administration of nicotine has anti-inflammatory effects in a mouse model of hypersensitivity pneumonitis, reduces the incidence of type 1 (autoimmune) diabetes and ulcerative colitis (1,21,24), and improves survival in experimental sepsis (27). Moreover, dimethylphenylpiperazinium (DMPP), a synthetic nicotinic acetylcholine receptor (nAChR) agonist, reduces airway inflammation as well as the increase in airway resistance in a mouse model of asthma (2). Finally, both nAChR agonists nicotine and DMPP have protective effects on early phase hepatic ischemia-reperfusion injury (6,27).…”