Phospholipase A2 Activation by Poultry Particulate Matter is Mediated Through Extracellular Signal-Regulated Kinase in Lung Epithelial Cells: Regulation of Interleukin-8 Release

Abstract

The mechanisms of poultry particulate matter (PM)-induced agricultural respiratory disorders are not thoroughly understood. Hence, it is hypothesized in this article that poultry PM induces the release of interleukin-8 (IL-8) by lung epithelial cells that is regulated upstream by the concerted action of cytosolic phospholipase A2 (cPLA2) and extracellular signal-regulated kinase (ERK). To test this hypothesis, the widely used cultured human lung epithelial cells (A549) were chosen as the model system. Poultry PM caused a significant activation of PLA2 in A549 cells, which was attenuated by AACOCF3 (cPLA2 inhibitor) and PD98059 (ERK-1/2 upstream inhibitor). Poultry PM induced upstream ERK-1/2 phosphorylation and downstream cPLA2 serine phosphorylation, in a concerted fashion, in cells with enhanced association of ERK-1/2 and cPLA2. The poultry PM-induced cPLA2 serine phosphorylation and IL-8 release were attenuated by AACOCF3, PD98059, and by transfection with dominant-negative ERK-1/2 DNA in cells. The poultry PM-induced IL-8 release by the bone marrow-derived macrophages of cPLA2 knockout mice was significantly lower. For the first time, this study demonstrated that the poultry PM-induced IL-8 secretion by human lung epithelial cells was regulated by cPLA2 activation through ERK-mediated serine phosphorylation, suggesting a mechanism of airway inflammation among poultry farm workers.

Pentalinon andrieuxii Root Extract is Effective in the Topical Treatment of Cutaneous Leishmaniasis Caused by Leishmania mexicana

“…mexicana parasite that could lead to the observed immunomodulation and antileishmanial actions caused by PARE. Lipid signaling pathway mediated by phospholipase A 2 has been established as a crucial step in the upstream regulation of cytokine release by the lung epithelial cells and macrophages (Kotha et al ., ). Therefore, it is conceivable that PARE containing the lipophilic molecules could have caused immunomodulation and antileishmanial actions through the (i) alterations of the lipid composition of the membranes of macrophages and the parasite thus leading to the changes in the membrane phase‐transition and activation of receptors towards modulation of cytokine synthesis and secretion in macrophages and parasite killing and (ii) activation of lipid signaling cascades involving phospholipases that could cause formation of bioactive lipids in the host macrophage and parasite leading to immunomodulation and antileishmanial actions, respectively.…”