A fucose specific lectin from Aspergillus flavus induced interleukin-8 expression is mediated by mitogen activated
Abstract:
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.
Insights
A novel fucose-specific lectin from Aspergillus flavus (FFL) triggers immune responses by activating the p38 MAPK pathway, leading to increased interleukin-8 (IL-8) production. This study reveals a key mechanism in host-fungus interactions.
Area of Science:
- Mycology
- Immunology
- Molecular Biology
Background:
- Aspergillus flavus is an opportunistic fungus causing invasive allergic diseases, particularly in immunocompromised individuals.
- Fungal lectins mediate interactions between pathogenic fungi and human hosts.
- Understanding these interactions is crucial for developing targeted therapies.
Purpose of the Study:
- To isolate and characterize a fucose-specific lectin from Aspergillus flavus.
- To investigate the lectin's role in modulating host immune responses, specifically cytokine induction.
- To elucidate the signaling pathways involved in the lectin-host cell interaction.
Main Methods:
- Isolation and purification of L-fucose specific lectin from A. flavus (FFL) using chromatography.
- Assay of hemagglutination activity with various sugars.
- Treatment of human cell lines (L-132 and U937) with FFL to assess cytotoxicity and proinflammatory effects.
- Analysis of cytokine expression (IL-8) and activation of signaling pathways (p38 MAPK, AP-1, c-Jun).
Main Results:
- A homogeneous L-fucose specific lectin (FFL) was isolated from A. flavus, exhibiting specific hemagglutination activity.
- FFL induced dose-dependent expression of the proinflammatory cytokine interleukin-8 (IL-8) in human cell lines.
- FFL-induced IL-8 production was mediated by the p38 MAPK pathway, leading to c-Jun activation and subsequent transcriptional regulation.
Conclusions:
- The study identified a fucose-specific lectin from A. flavus (FFL) that activates key inflammatory signaling pathways.
- FFL plays a role in modulating immune responses during host-pathogen interactions via the p38 MAPK/AP-1/IL-8 axis.
- This lectin-mediated mechanism offers a potential target for therapeutic interventions against Aspergillus flavus infections.
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