Interleukin-17 stimulates inducible nitric oxide synthase activation in rodent astrocytes

Trajkovič, Vladimir; Stošić‐Grujičić, Stanislava; Samardžić, Tatjana; Marković, Miloš; Miljković, Danijela; Ramić, Zorica; Stojković, Marija Mostarica

doi:10.1016/s0165-5728(01)00391-5

Cited by 91 publications

(67 citation statements)

References 40 publications

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“…The dominant role of IL-17RA signaling may lie in the fact that IL-17 synergizes potently with other inflammatory cytokines, particularly TNF␣ and IL-1␤. 14,55,77,78 Thus, while IL-17RA-mediated signals may appear to be redundant with those of TNF␣ and IL-1␤ in vitro, the amplifying effects of IL-17 are essential for an effective immune response in vivo. 79 While chemokine expression and neutrophil migration is impaired in IL-17RA KO mice, there may be defects in other arms of the immune system as well.…”

Section: Discussionmentioning

confidence: 99%

An essential role for IL-17 in preventing pathogen-initiated bone destruction: recruitment of neutrophils to inflamed bone requires IL-17 receptor–dependent signals

Ruddy

Wong

et al. 2007

Blood

313

304

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IL-17 and its receptor are founding members of a novel family of inflammatory cytokines. IL-17 plays a pathogenic role in rheumatoid arthritis (RA)–associated bone destruction. However, IL-17 is also an important regulator of host defense through granulopoiesis and neutrophil trafficking. Therefore, the role of IL-17 in pathogen-initiated bone loss was not obvious. The most common form of infection-induced bone destruction occurs in periodontal disease (PD). In addition to causing significant morbidity, PD is a risk factor for atherosclerotic heart disease and chronic obstructive pulmonary disease (COPD). Similar to RA, bone destruction in PD is caused by the immune response. However, neutrophils provide critical antimicrobial defense against periodontal organisms. Since IL-17 is bone destructive in RA but a key regulator of neutrophils, we examined its role in inflammatory bone loss induced by the oral pathogen Porphyromonas gingivalis in IL-17RA–deficient mice. These mice showed enhanced periodontal bone destruction, suggesting a bone-protective role for IL-17, reminiscent of a neutrophil deficiency. Although IL-17RA–deficient neutrophils functioned normally ex vivo, IL-17RA knock-out (IL-17RAKO) mice exhibited reduced serum chemokine levels and concomitantly reduced neutrophil migration to bone. Consistently, CXCR2KO mice were highly susceptible to alveolar bone loss; interestingly, these mice also suggested a role for chemokines in maintaining normal bone homeostasis. These results indicate a nonredundant role for IL-17 in mediating host defense via neutrophil mobilization.

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Section: Discussionmentioning

confidence: 99%

An essential role for IL-17 in preventing pathogen-initiated bone destruction: recruitment of neutrophils to inflamed bone requires IL-17 receptor–dependent signals

Ruddy

Wong

et al. 2007

Blood

313

304

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“…Other cytokines (e.g., TNF-α) usually induce iNOS in conjunction with IL-1β or IFN-γ. Although IFN-γ alone is sufficient to induce iNOS in rat and mouse primary microglia (64,138), no such effect has been reported so far in human primary microglia. In fact, we have found that different cytokines alone or in combination are also unable to induce the production of NO in human fetal microglia (unpublished observation).…”

Section: Cytokinesmentioning

confidence: 94%

Regulation of Inducible Nitric Oxide Synthase Gene in Glial Cells

Saha

Pahan

2006

Antioxidants & Redox Signaling

302

264

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Elevated levels of NO produced within the central nervous system (CNS) are associated with the pathogenesis of neuroinflammatory and neurodegenerative human diseases such as multiple sclerosis, HIV dementia, brain ischemia, trauma, Parkinson's disease, and Alzheimer's disease. Resident glial cells in the CNS (astroglia and microglia) express inducible nitric oxide synthase (iNOS) and produce high levels of NO in response to a wide variety of proinflammatory and degenerative stimuli. Although pathways resulting in the expression of iNOS may vary in two different glial cells of different species, the intracellular signaling events required for the expression of iNOS in these cells are slowly becoming clear. Various signaling cascades converge to activate several transcription factors that control the transcription of iNOS in glial cells. The present review summarizes different results and discusses current understandings about signaling mechanisms for the induction of iNOS expression in activated glial cells. A complete understanding of the regulation of iNOS expression in glial cells is expected to identify novel targets for therapeutic intervention in NO-mediated neurological disorders.

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“…Nitric oxide (NO) is an important inflammatory second messenger, and pathological NO is generated by inducible NO synthase (iNOS) during inflammation. IL-17A triggers a dose-and time-dependent expression of iNOS and concomitant increase in NO in various cell types [98,100,101]. The acute phase protein 24p3/Lipocalin 2 exhibits potent antibacterial activities by competing with bacterial siderophores to limit bacterial intake of free iron [102].…”

Section: Il-17 Regulates Inflammatory Genes Through Synergistic Signamentioning

confidence: 99%

Structure–function relationships in the IL-17 receptor: Implications for signal transduction and therapy

Shen¹,

Gaffen²

2008

Cytokine

232

245

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IL-17 is the defining cytokine of a newly-described "Th17" population that plays critical roles in mediating inflammation and autoimmunity. The IL-17/IL-17 receptor superfamily is the most recent class of cytokines and receptors to be described, and until recently very little was known about its function or molecular biology. However, in the last year important new insights into the composition and dynamics of the receptor complex and mechanisms of downstream signal transduction have been made, which will be reviewed here.

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Interleukin-17 stimulates inducible nitric oxide synthase activation in rodent astrocytes

Cited by 91 publications

References 40 publications

An essential role for IL-17 in preventing pathogen-initiated bone destruction: recruitment of neutrophils to inflamed bone requires IL-17 receptor–dependent signals

An essential role for IL-17 in preventing pathogen-initiated bone destruction: recruitment of neutrophils to inflamed bone requires IL-17 receptor–dependent signals

Regulation of Inducible Nitric Oxide Synthase Gene in Glial Cells

Structure–function relationships in the IL-17 receptor: Implications for signal transduction and therapy

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