Soluble cell wall beta-glucan of Candida induces/enhances apoptosis and oxidative stress in murine lung.
The bioactivity of cell wall component(s) of fungi has not been fully investigated, especially in vivo. We have successfully extracted a soluble cell wall beta-glucan from C. albicans (CSBG), and shown that pulmonary exposure to CSBG induces lung inflammation in mice. CSBG-induced lung inflammation was concomitant with the nuclear translocation of signal transducer and activator of transcription (STAT)6 and enhanced lung expression of various cytokines and chemokines. However, the effects of CSBG on the murine respiratory system and their mechanisms have not been fully investigated. In this study, we further explored the effects of pulmonary exposure to CSBG on lung pathophysiology in terms of the induction of apoptosis and enhancement of oxidative stress. ICR mice were intratracheally instilled with vehicle, CSBG, or structurally degraded products of CSBG by formic acid (DEG-CSBG), and 24 h later, the lungs were isolated and evaluated for apoptosis by the TUNEL assay and oxidative stress by immunohistochemistry of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a proper marker of the oxidative DNA damage. In another experiment, the mice were sacrificed and lungs were isolated 4 h after the instillation with vehicle or CSBG for evaluation of transcriptional level of heme oxygenase (HO)-1, a stress responsive protein. Pulmonary exposure to CSBG significantly induced apoptosis and enhanced the formation of 8-OHdG in the lung parenchyma as compared to vehicle or DEG-CSBG exposure. CSBG significantly induced HO-1 in the lung. Taken together, CSBG induces/enhances apoptosis and oxidative stress in the lung in association with lung inflammation/injury.
Inoue
Ken-ichiro
K
Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan. inoue.kenichirou@nies.go.jp
Takano
Hirohisa
H
Oda
Toshio
T
Yanagisawa
Rie
R
Tamura
Hiroshi
H
Adachi
Yoshiyuki
Y
Ishibashi
Ken-ichi
K
Ohno
Naohito
N
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002176:Candida albicans / Q000166:cytology*; D002473:Cell Wall / Q000737:chemistry*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects*; D012995:Solubility; D047071:beta-Glucans / Q000494:pharmacology*
D047071:beta-Glucans; D000080242:8-Hydroxy-2'-Deoxyguanosine; D051547:Heme Oxygenase-1; D003849:Deoxyguanosine