A Role for Il-18 in Human Neutrophil Apoptosis

Hirata, Junichi; Kotani, Joji; Aoyama, Masayuki; Kashiwamura, Shin-ichiro; Ueda, Hiroyuki; Kuroda, Yasuhiro; Usami, Makoto; Okamura, Haruki; Marukawa, Seishiro

doi:10.1097/shk.0b013e31817c0c69

Cited by 30 publications

(29 citation statements)

References 47 publications

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“…Although we find an increase in p38 MAPK phosphorylation in C. pneumoniae-infected neutrophils, p38 MAPK activation does not appear to contribute to survival effect on infected neutrophils since treatment with the p38 MAPK inhibitor does not reverse apoptosis delay in infected neutrophils. This observation is in line with a previous report in which the p38 MAPK inhibitor SB203580 could not reverse the apoptosis delay in IL-18-treated neutrophils (Hirata et al, 2008). Therefore, p38 MAPK appears to be of limited importance as survival pathway in primary human neutrophils.…”

Section: Discussionsupporting

confidence: 91%

Mechanisms of apoptosis inhibition in Chlamydia pneumoniae-infected neutrophils

Sarkar¹,

Möller²,

Bhattacharyya³

et al. 2015

International Journal of Medical Microbiology

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Section: Discussionsupporting

confidence: 91%

Mechanisms of apoptosis inhibition in Chlamydia pneumoniae-infected neutrophils

Sarkar¹,

Möller²,

Bhattacharyya³

et al. 2015

International Journal of Medical Microbiology

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“…The role of IL-18 on regulating apoptosis is controversial and seems to be driven by cell type-specific mechanisms. IL-18 inhibits neutrophil apoptosis (19) while it accelerates cell death in chondrocytes (22) and renal tubular cells (54). Secondly, we found that immobilized IL-18 stimulates macrophage adhesion to fibrinogen in a Mac-1-dependent fashion.…”

Section: Discussionmentioning

confidence: 69%

Macrophage-derived IL-18 and increased fibrinogen deposition are age-related inflammatory signatures of vascular remodeling

Rodriguez-Menocal

Faridi

Martinez

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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Padron RI. Macrophage-derived IL-18 and increased fibrinogen deposition are age-related inflammatory signatures of vascular remodeling. Am J Physiol Heart Circ Physiol 306: H641-H653, 2014. First published January 10, 2014; doi:10.1152/ajpheart.00641.2013.-Aging has been associated with pathological vascular remodeling and increased neointimal hyperplasia. The understanding of how aging exacerbates this process is fundamental to prevent cardiovascular complications in the elderly. This study proposes a mechanism by which aging sustains leukocyte adhesion, vascular inflammation, and increased neointimal thickness after injury. The effect of aging on vascular remodeling was assessed in the rat balloon injury model using microarray analysis, immunohistochemistry, and LINCOplex assays. The injured arteries in aging rats developed thicker neointimas than those in younger animals, and this significantly correlated with a higher number of tissue macrophages and increased vascular IL-18. Indeed, IL-18 was 23-fold more abundant in the injured vasculature of aged animals compared with young rats, while circulating levels were similar in both groups of animals. The depletion of macrophages in aged rats with clodronate liposomes ameliorated vascular accumulation of IL-18 and significantly decreased neointimal formation. IL-18 was found to inhibit apoptosis of vascular smooth muscle cells (VSMC) and macrophages, thus favoring both the formation and inflammation of the neointima. In addition, injured arteries of aged rats accumulated 18-fold more fibrinogen-␥ than those of young animals. Incubation of rat peritoneal macrophages with immobilized IL-18 increased leukocyte adhesion to fibrinogen and suggested a proinflammatory positive feedback loop among macrophages, VSMC, and the deposition of fibrinogen during neointimal hyperplasia. In conclusion, our data reveal that concentration changes in vascular cytokine and fibrinogen following injury in aging rats contribute to local inflammation and postinjury neointima formation. inflammation; vascular injury; aging; neointima; vascular smooth muscle cells AGING IS RECOGNIZED AS A MAJOR and independent risk factor for the development of vascular restenosis (29). This risk can be explained by profound, age-dependent changes in vascular structure and physiology that lead to endothelial dysfunction (18) and a chronic inflammatory stage (53), which impair healing and render a vascular system prone to develop occlusive neointimas in response to injury. However, even when this notion is largely accepted, the mechanisms by which aging alters vascular physiology and repair have remained understudied to date.The process of aging increases and sustains inflammation within the vascular wall (52). Macrophages are commonly recognized as the most important cell type in the chronicity of this process (37). Indeed, inflammation in arteries of aged individuals is evidenced by an excessive accumulation of macrophages in the inner layer of the arterial wall (intima), and this occurs in the presence o...

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“…4 Arndt et al reported that IL-18 may play a role in modulating the development of acute lung injury during endotoxemia. 5 As we reported that IL-18 delayed human neutrophil apoptosis in vitro, 6 the effect of IL-18 on neutrophil apoptosis may be a key factor in acute lung injury.…”

Section: Introductionmentioning

confidence: 99%

Role of endogenous IL‐18 in the lung during endotoxin‐induced systemic inflammation

Takahara

Ishikawa

Shuno

et al. 2013

Acute Medicine & Surgery

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Background: Overactivated neutrophils are causes of acute lung injury, which is a major clinical problem with significant morbidity and mortality in sepsis. Serum interleukin (IL)-18 levels correspond to severity of systemic inflammation.Aim: To elucidate the roles of endogenous IL-18 in lung injury during endotoxin-induced systemic inflammation. Methods: Wild-type (WT) and IL-18 gene knockout (KO) mice were injected with lipopolysaccharide (40 mg/kg) intraperitoneally and killed. Lungs were collected at 0 and 12 h to assess mRNA for intercellular adhesion molecule (ICAM)-1, inducible nitric oxide synthase, myeloperoxidase, immunohistochemistry (cleaved caspase-3, 8-hydroxy-2-deoxyguanosine), and wet/dry ratio. Blood was collected at 0, 1, 12, 18, and 24 h to assess plasma cytokine levels. Results:The survival rates at 24 h were approximately 43% and 76% in the WT and KO mice, respectively. Plasma IL-18 levels were induced time-dependently only in the WT mice. Plasma interferon-γ levels were significantly higher in the WT than in the KO mice at 12 h, but IL-6 and tumor necrosis factor-α levels did not differ between the WT and KO mice. At 12 h, the WT mice showed higher myeloperoxidase activity (P < 0.05), ICAM-1, and wet/dry ratios than KO mice. Cleaved caspase-3 positive neutrophils, which migrated in the lung interstitium, were lower in WT mice than in KO mice.Conclusions: Endogenous IL-18 induced neutrophil accumulation, accompanied by induction of ICAM-1 expression, inhibition of neutrophil apoptosis, and increased inducible nitric oxide synthase-induced oxidative tissue injury in the lung, leading to lung edema and poor outcome during endotoxemia.

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A Role for Il-18 in Human Neutrophil Apoptosis

Cited by 30 publications

References 47 publications

Mechanisms of apoptosis inhibition in Chlamydia pneumoniae-infected neutrophils

Mechanisms of apoptosis inhibition in Chlamydia pneumoniae-infected neutrophils

Macrophage-derived IL-18 and increased fibrinogen deposition are age-related inflammatory signatures of vascular remodeling

Role of endogenous IL‐18 in the lung during endotoxin‐induced systemic inflammation

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