Pulmonary exposure to soluble cell wall beta-(1, 3)-glucan of aspergillus induces proinflammatory response in mice
K Inoue1, E Koike, R Yanagisawa
1Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan. inoue.kenichirou@nies.go.jp
Abstract:
Compared to the significant immunomodulation of cell wall component(s) of bacterium such as lipopolysaccharide (E. Coli), that of pathogenic fungi has not been well elucidated, especially in vivo. Furthermore, although it has been implied that beta-(1, 3)-glucan of fungi possesses various biological activities, the impacts of the component have not been properly clarified, possibly due to its insolubility in water and alkali solutions. Previously, we isolated a soluble type of beta-(1, 3) -glucan from Aspergillus (referred to as ASBG). The present study investigated the effects of a single pulmonary exposure to ASBG on the immune (proinflammatory) responses in naïve mice. ASBG (12.5-100micorg/animal) exposure Induced neutrophilic lung inflammation with an enhanced local expression of proinflammatory cytokines such as interleukin (IL)-1beta and chemokines such as macrophage inflammatory protein -1a, and keratinocyte-derived chemoattractant in a dose-dependent fashion with overall trends. On the other hand, ASBG at relatively lower doses significantly amplified the lung expression of IL-2, IL-6, and IL-12 as compared with vehicle. ASBG significantly induced pulmonary edema. Furthermore, ASBG augmented the nuclear translocation of nuclear factor (NF)-kB and its binding capacity to the promoter site of DNA in the lung homogenate. These results suggest that pulmonary exposure to ASBG confers lung inflammation, at least partly, via the enhanced local expression of proinflammatory cytokines, likely through NF-kB-dependent pathway.
Insights
Pulmonary exposure to soluble beta-(1,3)-glucan from Aspergillus (ASBG) induced lung inflammation in mice. This immune response involved increased proinflammatory cytokines and nuclear factor-kappa B activation.
Area of Science:
- Immunology
- Mycology
- Pulmonary Medicine
Background:
- Fungal cell wall components, particularly beta-(1,3)-glucan, are known to possess immunomodulatory activities, but their in vivo effects remain poorly understood.
- The insolubility of beta-(1,3)-glucan has hindered comprehensive investigation of its biological impacts.
- A soluble form of beta-(1,3)-glucan from Aspergillus (ASBG) was previously isolated.
Purpose of the Study:
- To investigate the effects of pulmonary exposure to ASBG on immune responses in naive mice.
- To elucidate the mechanisms underlying ASBG-induced lung inflammation.
Main Methods:
- Mice were exposed to varying doses of ASBG via pulmonary route.
- Lung inflammation markers, including cytokine and chemokine expression, were assessed.
- Nuclear factor-kappa B (NF-kB) activation was evaluated in lung homogenates.
Main Results:
- ASBG exposure induced dose-dependent neutrophilic lung inflammation.
- Increased expression of proinflammatory cytokines (IL-1beta, IL-2, IL-6, IL-12) and chemokines (macrophage inflammatory protein-1a, keratinocyte-derived chemoattractant) was observed.
- Pulmonary edema and augmented NF-kB nuclear translocation and DNA binding capacity were noted.
Conclusions:
- Pulmonary exposure to ASBG triggers significant lung inflammation in mice.
- The inflammatory response is mediated, at least in part, by enhanced local expression of proinflammatory cytokines via an NF-kB-dependent pathway.
