A fucose specific lectin from Aspergillus flavus induced interleukin-8 expression is mediated by mitogen activated protein kinase p38.
Aspergillus flavus is an ubiquitous, opportunistic fungus responsible to cause invasive fungal allergic diseases, including bronchopulmonary invasive aspergillosis in persons with altered immune function. Lectins have been implicated as interaction mediators between the pathogenic fungi and human host. We isolated L-fucose specific lectin from A. flavus (FFL) and purified it to homogeneity with a combination of ion exchange and hydrophobic interaction chromatography methods. Its hemagglutination activity was significantly inhibited by 125 μM L-fucose as compared to other sugars and sugar derivatives. We, then used human cell line L-132, and U937 cell line to explore the possible cytotoxicity and proinflammatory effect of this fucose-specific lectin. The lectin induced the expression of proinflammatory cytokine interleukin-8 (IL-8) in a dose-dependent manner, and it was found to be associated with the p38 mitogen activated protein kinase (MAPK). The p38MAPK signalling pathway regulates the transcription factor activator protein-1 (AP-1) activity, which is 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 p38MAPK upon the FFL treatment in L-132 cells. Finally, inhibition of p38MAPK by a specific inhibitor attenuates the c-Jun, suggesting the p38MAPK involvement in the c-Jun activation, which in turn transcriptionally activates the induction of IL-8 in response to the lectin. Thus, this study showed a potential lectin-mediated mechanism to modulate the immune response during host-fungus interactions.
Md Sajid
MS
Ghufran
Krishna
K
Ghosh
Santosh R
SR
Kanade
D001231:Aspergillus flavus / Q000737:chemistry / Q000276:immunology*; D002460:Cell Line; D015870:Gene Expression; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D037102:Lectins / Q000302:isolation & purification / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
C508606:CXCL8 protein, human; D016209:Interleukin-8; D037102:Lectins; C064549:lectin, Aleuria aurantia; D048051:p38 Mitogen-Activated Protein Kinases
AP-1; Aspergillus flavus; fucose; interleukin-8; lectin; p38MAPK