Limits...
The role of nitric oxide in mycobacterial infections.

Yang CS, Yuk JM, Jo EK - Immune Netw (2009)

Bottom Line: Although tuberculosis poses a significant health threat to the global population, it is a challenge to develop new and effective therapeutic strategies.Nitric oxide (NO) and inducible NO synthase (iNOS) are important in innate immune responses to various intracellular bacterial infections, including mycobacterial infections.We also discuss the specific roles of NO in the central nervous system and lung epithelial cells during mycobacterial infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon 301-747, Korea.

ABSTRACT
Although tuberculosis poses a significant health threat to the global population, it is a challenge to develop new and effective therapeutic strategies. Nitric oxide (NO) and inducible NO synthase (iNOS) are important in innate immune responses to various intracellular bacterial infections, including mycobacterial infections. It is generally recognized that reactive nitrogen intermediates play an effective role in host defense mechanisms against tuberculosis. In a murine model of tuberculosis, NO plays a crucial role in antimycobacterial activity; however, it is controversial whether NO is critically involved in host defense against Mycobacterium tuberculosis in humans. Here, we review the roles of NO in host defense against murine and human tuberculosis. We also discuss the specific roles of NO in the central nervous system and lung epithelial cells during mycobacterial infection. A greater understanding of these defense mechanisms in human tuberculosis will aid in the development of new strategies for the treatment of disease.

No MeSH data available.


Related in: MedlinePlus

Yang et al. Synthesis, regulation, and antimycobacterial function of NO in mycobacterial infection. Activated inducible nitric oxide synthase (iNOS) produces Nω-OH-L-arginine from L-arginine, and then Nω-OH-L-arginine is transduced to form NO and L-citruline. Synthesis of NO and reactive nitrogen oxides (RNI) are positively regulated by Th1 cytokines, whereas they are negatively regulated by Th2 cytokines. Produced NO and RNIs, which combined with NO and O2-, can directly kill intracellular MTB in the infected cells (including macrophages, epithelial and glial cells), although the action of NO is dependent on the species and specific cell types.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2803309&req=5

Figure 1: Yang et al. Synthesis, regulation, and antimycobacterial function of NO in mycobacterial infection. Activated inducible nitric oxide synthase (iNOS) produces Nω-OH-L-arginine from L-arginine, and then Nω-OH-L-arginine is transduced to form NO and L-citruline. Synthesis of NO and reactive nitrogen oxides (RNI) are positively regulated by Th1 cytokines, whereas they are negatively regulated by Th2 cytokines. Produced NO and RNIs, which combined with NO and O2-, can directly kill intracellular MTB in the infected cells (including macrophages, epithelial and glial cells), although the action of NO is dependent on the species and specific cell types.

Mentions: Th1 cytokines such as IFN-γ, IL-1β, and TNF-α stimulate the expression of macrophage iNOS, leading to NO production. In contrast, under the influence of Th2 cytokines such as IL-4, IL-10, and IL-13, arginine is depleted by arginases (8-10). NO is one of several RNIs with antimicrobial activity (18,25). The increase in RNIs is mediated through reactive nitrogen oxides (e.g., peroxynitrite (ONOO-)) generated by the reaction of NO with O2- (13,24) (Fig. 1). NO and RNIs can modify bacterial DNA, proteins, and lipids in both the microbe and host. NO can also deaminate and directly damage bacterial DNA by generating abasic sites and strand breaks (7). Other potential killing mechanisms by NO include interactions with accessory protein targets such as iron-sulfur groups, heme groups, thiols, aromatic or phenolic residues, tyrosyl radicals, and amines. These reactions result in enzymatic inactivation and/or other protein malfunctions (26).


The role of nitric oxide in mycobacterial infections.

Yang CS, Yuk JM, Jo EK - Immune Netw (2009)

Yang et al. Synthesis, regulation, and antimycobacterial function of NO in mycobacterial infection. Activated inducible nitric oxide synthase (iNOS) produces Nω-OH-L-arginine from L-arginine, and then Nω-OH-L-arginine is transduced to form NO and L-citruline. Synthesis of NO and reactive nitrogen oxides (RNI) are positively regulated by Th1 cytokines, whereas they are negatively regulated by Th2 cytokines. Produced NO and RNIs, which combined with NO and O2-, can directly kill intracellular MTB in the infected cells (including macrophages, epithelial and glial cells), although the action of NO is dependent on the species and specific cell types.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2803309&req=5

Figure 1: Yang et al. Synthesis, regulation, and antimycobacterial function of NO in mycobacterial infection. Activated inducible nitric oxide synthase (iNOS) produces Nω-OH-L-arginine from L-arginine, and then Nω-OH-L-arginine is transduced to form NO and L-citruline. Synthesis of NO and reactive nitrogen oxides (RNI) are positively regulated by Th1 cytokines, whereas they are negatively regulated by Th2 cytokines. Produced NO and RNIs, which combined with NO and O2-, can directly kill intracellular MTB in the infected cells (including macrophages, epithelial and glial cells), although the action of NO is dependent on the species and specific cell types.
Mentions: Th1 cytokines such as IFN-γ, IL-1β, and TNF-α stimulate the expression of macrophage iNOS, leading to NO production. In contrast, under the influence of Th2 cytokines such as IL-4, IL-10, and IL-13, arginine is depleted by arginases (8-10). NO is one of several RNIs with antimicrobial activity (18,25). The increase in RNIs is mediated through reactive nitrogen oxides (e.g., peroxynitrite (ONOO-)) generated by the reaction of NO with O2- (13,24) (Fig. 1). NO and RNIs can modify bacterial DNA, proteins, and lipids in both the microbe and host. NO can also deaminate and directly damage bacterial DNA by generating abasic sites and strand breaks (7). Other potential killing mechanisms by NO include interactions with accessory protein targets such as iron-sulfur groups, heme groups, thiols, aromatic or phenolic residues, tyrosyl radicals, and amines. These reactions result in enzymatic inactivation and/or other protein malfunctions (26).

Bottom Line: Although tuberculosis poses a significant health threat to the global population, it is a challenge to develop new and effective therapeutic strategies.Nitric oxide (NO) and inducible NO synthase (iNOS) are important in innate immune responses to various intracellular bacterial infections, including mycobacterial infections.We also discuss the specific roles of NO in the central nervous system and lung epithelial cells during mycobacterial infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon 301-747, Korea.

ABSTRACT
Although tuberculosis poses a significant health threat to the global population, it is a challenge to develop new and effective therapeutic strategies. Nitric oxide (NO) and inducible NO synthase (iNOS) are important in innate immune responses to various intracellular bacterial infections, including mycobacterial infections. It is generally recognized that reactive nitrogen intermediates play an effective role in host defense mechanisms against tuberculosis. In a murine model of tuberculosis, NO plays a crucial role in antimycobacterial activity; however, it is controversial whether NO is critically involved in host defense against Mycobacterium tuberculosis in humans. Here, we review the roles of NO in host defense against murine and human tuberculosis. We also discuss the specific roles of NO in the central nervous system and lung epithelial cells during mycobacterial infection. A greater understanding of these defense mechanisms in human tuberculosis will aid in the development of new strategies for the treatment of disease.

No MeSH data available.


Related in: MedlinePlus