Effect of sodium butyrate on reactive oxygen species generation by human neutrophils.
BACKGROUND
Short-chain fatty acids enema has been shown to be effective in the treatment of ulcerative colitis (UC). However, the mechanisms that lead to this response have not been well characterized. The aims of this study were to investigate the effect sodium butyrate has on reactive oxygen species (ROS) generation by human neutrophils, which are responsible for mucosal injury.


METHODS
Human neutrophils incubated with or without sodium butyrate were stimulated with opsonized zymosan (OZ) or phorbol myristate acetate (PMA). ROS generation was largely differentiated with flow cytometry assays of hydroethidine oxidation and dichlorofluorescein oxidation for superoxide anion and hydrogen peroxide respectively, and luminol-dependent chemiluminescence for myeloperoxidase-mediated oxidants.


RESULTS
Sodium butyrate (up to 50 mM) did not alter hydroethidine oxidation upon stimulation of the OZ or PMA. However, sodium butyrate at a concentration of 25 mM elevated dichlorofluorescein oxidation to 125 + 8% (P = 0.028) of control upon stimulation of OZ and to 191 +/- 30% (P = 0.0016) upon stimulation of PMA. Contrary to these results, sodium butyrate greatly inhibited chemiluminescence responses in a dose-dependent manner. The inhibition by 50 mM sodium butyrate was 61 +/- 6% upon OZ and 71 +/- 9% upon PMA, respectively.


CONCLUSIONS
These data indicate that sodium butyrate up-regulates hydrogen peroxide generation but down-regulates generation of myeloperoxidase-mediated oxidants, the latter being more potent in killing microorganisms and in inducing tissue injury. A possible mechanism is suggested whereby sodium butyrate may inhibit myeloperoxidase activity and hence attenuate the destructive activities of neutrophils in UC.
Liu
Q
Q
Dept. of Hygiene, Hirosaki University School of Medicine, Aomori, Japan. liuqiang@cc.hirosaki-u.ac.jp
Shimoyama
T
T
Suzuki
K
K
Umeda
T
T
Nakaji
S
S
Sugawara
K
K
D002087:Butyrates / Q000494:pharmacology* / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005434:Flow Cytometry; D006801:Humans; D006861:Hydrogen Peroxide / Q000276:immunology / Q000378:metabolism*; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D008163:Luminescent Measurements; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
D002087:Butyrates; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D009195:Peroxidase