A toxic gas eases IBD
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《实验药学杂志》
Inhaled carbon monoxide induces the intestinal expression of heme oxygenase-1 (dark brown) and soothes colitis.
A study on page 1703 might help explain why active smokers rarely suffer from an inflammatory bowel disease (IBD) known as ulcerative colitis. Hegazi and colleagues show that carbon monoxide (CO) gas, a component of cigarette smoke, shuts down the production of a disease-promoting cytokine, thus easing chronic bowel inflammation in mice.
CO is both a toxic air pollutant and a normal byproduct of cellular heme metabolism. Although CO's asphyxiant properties have earned it a bad reputation, the ubiquitous tissue expression of the natural CO-producing enzyme heme oxygenase-1 (HO-1) suggests that the effects of CO must not be all bad.
Indeed, recent studies have shown that CO, at least at low concentrations, has a redeeming quality: it acts as an antiinflammatory agent. Low dose inhaled CO is therapeutic in many acute disease models including bacterial sepsis, organ transplantation, and vascular injury. Normally, HO-1 expression (and thus CO production) is induced under conditions of cellular stress, such as infection or oxygen deprivation, probably to limit the adverse effects of stress-induced inflammation.
The effects of CO on chronic inflammation, however, had not been studied. Here, Hegazi and colleagues show that CO exposure also inhibits chronic intestinal inflammation in mice. Exogenous CO treatment induced the expression of HO-1, either directly or indirectly, which in turn limited the intestinal production of the inflammation-inducing cytokine interleukin (IL)-12. In macrophages, HO-1 inhibited the expression of the transcription factor IRF-8 (interferon regulatory factor-8), which normally drives the synthesis of IL-12 in response to bacterial lipopolysaccharide and interferon-—a situation that mimics the stimulation of these cells in the inflamed intestine.
Although the induction of HO-1 is required for the therapeutic effects of CO in most disease models, this is the first study to identify IRF-8 as a target of HO-1–induced inhibition. How HO-1 represses IRF-8 expression remains to be determined.
Based on these results, the authors suggest that inhaled CO or agents that increase endogenous HO-1 activity might be therapeutic in patients with ulcerative colitis. However, nonsmokers with IBD shouldn't necessarily break out the Marlboros, as cigarette smoking is a risk factor not only for heart disease and cancer but also for Crohn's disease, another form of IBD.(Heather L. Van Epps)
A study on page 1703 might help explain why active smokers rarely suffer from an inflammatory bowel disease (IBD) known as ulcerative colitis. Hegazi and colleagues show that carbon monoxide (CO) gas, a component of cigarette smoke, shuts down the production of a disease-promoting cytokine, thus easing chronic bowel inflammation in mice.
CO is both a toxic air pollutant and a normal byproduct of cellular heme metabolism. Although CO's asphyxiant properties have earned it a bad reputation, the ubiquitous tissue expression of the natural CO-producing enzyme heme oxygenase-1 (HO-1) suggests that the effects of CO must not be all bad.
Indeed, recent studies have shown that CO, at least at low concentrations, has a redeeming quality: it acts as an antiinflammatory agent. Low dose inhaled CO is therapeutic in many acute disease models including bacterial sepsis, organ transplantation, and vascular injury. Normally, HO-1 expression (and thus CO production) is induced under conditions of cellular stress, such as infection or oxygen deprivation, probably to limit the adverse effects of stress-induced inflammation.
The effects of CO on chronic inflammation, however, had not been studied. Here, Hegazi and colleagues show that CO exposure also inhibits chronic intestinal inflammation in mice. Exogenous CO treatment induced the expression of HO-1, either directly or indirectly, which in turn limited the intestinal production of the inflammation-inducing cytokine interleukin (IL)-12. In macrophages, HO-1 inhibited the expression of the transcription factor IRF-8 (interferon regulatory factor-8), which normally drives the synthesis of IL-12 in response to bacterial lipopolysaccharide and interferon-—a situation that mimics the stimulation of these cells in the inflamed intestine.
Although the induction of HO-1 is required for the therapeutic effects of CO in most disease models, this is the first study to identify IRF-8 as a target of HO-1–induced inhibition. How HO-1 represses IRF-8 expression remains to be determined.
Based on these results, the authors suggest that inhaled CO or agents that increase endogenous HO-1 activity might be therapeutic in patients with ulcerative colitis. However, nonsmokers with IBD shouldn't necessarily break out the Marlboros, as cigarette smoking is a risk factor not only for heart disease and cancer but also for Crohn's disease, another form of IBD.(Heather L. Van Epps)