Cytokine expression in human monocyte cell line infected with Aspergillus flavus is mediated by MAPK

Abstract

Aspergillus flavus is liable to mediate immune response in a wide variety of cells by inducing varied host pathogen interactions, being the most etiological agent in India. The culture filtrate and spores of fungal species are implicated in the onset of allergic responses finally leading to the initiation of proinflammatory reactions. Human monocytic U937 cells were exposed to varying concentrations of culture filtrate and spores as well, to establish their cytotoxic role and proinflammatory effect. The expression of a wide array of proinflammatory cytokines, particularly interleukin-8 (IL-8), was found to be induced in a dose-dependent manner upon stimulation of cells. The upregulation of cytokine IL-8 was further shown to be associated with the regulation of signalling pathways mediated via p38 and one of its prime downstream target molecules, activator protein-1 (AP-1) transcription factor. The p38 mitogen-activated protein kinase (MAPK) signalling pathway regulates the transcription factor AP-1 activity, the integration point of many signals that can differentially affect the expression and transcriptional activity of a cell. We observed activation of c-Jun, a critical component of the AP-1 complex, mediated by p38 MAPK upon stimulation with the culture filtrate. Thus, this study showed a crucial role of culture filtrate and spores of A. flavus in mediating the immune responses by the secretion of proinflammatory cytokines. Abbreviations IL-8, Interleukin-8; TNF α, Tumor necrosis factor alpha; GM-CSF, Granulocyte macrophage colony stimulating factor.