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Synergistic proinflammatory interactions of microbial toxins and structural components characteristic to
M Korkalainen1, M Täubel1, J Naarala2
1Department of Health Protection, National Institute for Health and Welfare, Kuopio, Finland.
Abstract:
Indoor exposure to microbes and their structural and metabolic compounds is notoriously complex. To study proinflammatory interactions between the multiple microbial agents, macrophages derived from human THP-1 monocytic cells were exposed to several concentrations of microbial toxins alone (emodin, enniatin B, physcion, sterigmatocystin, valinomycin) and in combination with microbial structural components (bacterial lipopolysaccharide [LPS] or fungal β-glucan). While the expression of proinflammatory cytokines TNFα and IL-1β to single toxins alone was modest, low-dose co-exposure with structural components increased the responses of emodin, enniatin B, and valinomycin synergistically, both at the mRNA and protein level, as measured by RT-qPCR and ELISA, respectively. Co-exposure of toxins and β-glucan resulted in consistent synergistically increased expression of several inflammation-related genes, while some of the responses with LPS were also inhibitory. Co-exposure of toxins with either β-glucan or LPS induced also mitochondrial damage and autophagocytosis. The results demonstrate that microbial toxins together with bacterial and fungal structural components characteristic to moisture-damaged buildings can have drastic synergistic proinflammatory interactions at low exposure levels.
Insights
Indoor microbial toxins and structural components, like lipopolysaccharide (LPS) and β-glucan, can synergistically increase inflammation. Low-level co-exposure triggers significant proinflammatory responses and cellular damage in human macrophages.
Area of Science:
- Environmental microbiology
- Immunology
- Toxicology
Background:
- Indoor environments harbor complex mixtures of microbial agents.
- Microbial toxins and structural components are key players in indoor air quality and health.
- Understanding synergistic effects is crucial for assessing health risks.
Purpose of the Study:
- To investigate the proinflammatory interactions between microbial toxins and structural components.
- To determine the impact of co-exposure on macrophage responses.
- To assess cellular damage and inflammatory gene expression.
Main Methods:
- Human THP-1 monocytic cells were exposed to microbial toxins (emodin, enniatin B, physcion, sterigmatocystin, valinomycin) alone and with bacterial lipopolysaccharide (LPS) or fungal β-glucan.
- Messenger RNA (mRNA) and protein levels of proinflammatory cytokines (TNFα, IL-1β) were measured using RT-qPCR and ELISA.
- Mitochondrial damage and autophagocytosis were assessed.
Main Results:
- Low-dose co-exposure of toxins with LPS or β-glucan synergistically increased proinflammatory cytokine expression (TNFα, IL-1β) at both mRNA and protein levels.
- Co-exposure with β-glucan consistently upregulated inflammation-related genes, while LPS showed some inhibitory effects.
- Combined exposure induced mitochondrial damage and autophagocytosis.
Conclusions:
- Microbial toxins and structural components from environments like moisture-damaged buildings can cause significant synergistic proinflammatory interactions.
- These synergistic effects occur even at low exposure levels.
- The findings highlight the complex interplay of indoor microbes in triggering inflammatory responses and cellular damage.
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