Cyclooxygenase‐2 deficient mice are resistant to endotoxin‐induced inflammation and death

Ejima, Kuniaki; Layne, Matthew D.; Carvajal, Irvith M.; Kritek, Patricia; Baron, Rebecca M.; Chen, Yen Hsu; Saal, Jeffrey Vom; Levy, Bruce D.; Yet, Shaw Fang; Perrella, Mark A.

doi:10.1096/fj.02-1078fje

Cited by 115 publications

(112 citation statements)

References 49 publications

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“…The involvement of the COX pathway in inflammatory processes and modulation of immune responses is well established. In addition, the COX pathway has been implicated in modulating the host response to infection (5,7,8) and is a major target for the widely prescribed NSAIDs and the newer COX-2 inhibitors such as celecoxib and rofecoxib. Importantly, no studies to date have examined the relative effects of COX-1 and COX-2 in the host response to influenza viral infection.…”

Section: Discussionmentioning

confidence: 99%

“…The cyclooxygenase (COX) 3 enzymes, which catalyze the first step in the biosynthesis of prostaglandins from arachidonic acid, have specifically been implicated as being important in host responses to infection (5,7,8), and the ability of COX products to modulate inflammation and immune responses is well documented (9 -14). In humans, prostanoid production can be altered genetically via polymorphisms in the COX enzymes (15)(16)(17).…”

mentioning

confidence: 99%

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Contrasting Effects of Cyclooxygenase-1 (COX-1) and COX-2 Deficiency on the Host Response to Influenza A Viral Infection

Carey¹,

Bradbury²,

Seubert³

et al. 2005

The Journal of Immunology

102

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Influenza is a significant cause of morbidity and mortality worldwide despite extensive research and vaccine availability. The cyclooxygenase (COX) pathway is important in modulating immune responses and is also a major target of nonsteroidal anti-inflammatory drugs (NSAIDs) and the newer COX-2 inhibitors. The purpose of the present study was to examine the effect of deficiency of COX-1 or COX-2 on the host response to influenza. We used an influenza A viral infection model in wild type (WT), COX-1−/−, and COX-2−/− mice. Infection induced less severe illness in COX-2−/− mice in comparison to WT and COX-1−/− mice as evidenced by body weight and body temperature changes. Mortality was significantly reduced in COX-2−/− mice. COX-1−/− mice had enhanced inflammation and earlier appearance of proinflammatory cytokines in the BAL fluid, whereas the inflammatory and cytokine responses were blunted in COX-2−/− mice. However, lung viral titers were markedly elevated in COX-2−/− mice relative to WT and COX-1−/− mice on day 4 of infection. Levels of PGE2 were reduced in COX-1−/− airways whereas cysteinyl leukotrienes were elevated in COX-2−/− airways following infection. Thus, deficiency of COX-1 and COX-2 leads to contrasting effects in the host response to influenza infection, and these differences are associated with altered production of prostaglandins and leukotrienes following infection. COX-1 deficiency is detrimental whereas COX-2 deficiency is beneficial to the host during influenza viral infection.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Contrasting Effects of Cyclooxygenase-1 (COX-1) and COX-2 Deficiency on the Host Response to Influenza A Viral Infection

Carey¹,

Bradbury²,

Seubert³

et al. 2005

The Journal of Immunology

102

View full text Add to dashboard Cite

show abstract

“…We chose to colocalize several organ markers with infiltrating or activated resident immune cells as an indicator of the severity of organ damage. Hepatic activation of COX-2 can induce macrophage activation and recruitment, which are crucial in systemic cytokine and lipid mediator production at the onset of sepsis (22). A three-fold increase in infiltrating F4/80 + macrophages and activated Kupffer cells was seen in the LPS group compared with the vehicle control group (Figure 2A).…”

Section: Simvastatin and Dlgg Modulate Organ-specific Infiltration Ofmentioning

confidence: 98%

Simvastatin and a Plant Galactolipid Protect Animals from Septic Shock by Regulating Oxylipin Mediator Dynamics through the MAPK-cPLA2 Signaling Pathway

Apaya

Lin

Chiou

et al. 2015

Mol Med

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“…1A). COX-2-deficient mice and LXA 4 receptor (ALX)-transgenic (tg) mice were generated as previously described (18,19). All mice were maintained under specific pathogen-free conditions.…”

Section: Acid-initiated Acute Lung Injurymentioning

confidence: 99%

Cyclooxygenase 2 Plays a Pivotal Role in the Resolution of Acute Lung Injury

Fukunaga

Kohli

Bonnans

et al. 2005

The Journal of Immunology

Self Cite

245

253

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Acute lung injury (ALI) is a severe illness with excess mortality and no specific therapy. In its early exudative phase, neutrophil activation and accumulation in the lung lead to hypoxemia, widespread tissue damage, and respiratory failure. In clinical trials, inhibition of proinflammatory mediators has not proven effective. In this study, we pursued a new investigative strategy that emphasizes mediators promoting resolution from lung injury. A new spontaneously resolving experimental murine model of ALI from acid aspiration was developed to identify endogenous proresolving mechanisms. ALI increased cyclooxygenase 2 (COX-2) expression in murine lung. Selective pharmacologic inhibition or gene disruption of COX-2 blocked resolution of ALI. COX-2-derived products increased levels of the proresolving lipid mediators lipoxin A4 (LXA4) and, in the presence of aspirin, 15-epi-LXA4. Both LXA4 and 15-epi-LXA4 interact with the LXA4 receptor (ALX) to mediate anti-inflammatory actions. ALX expression was markedly induced by acid injury and transgenic mice with increased ALX expression displayed dramatic protection from ALI. Together, these findings indicate a protective role in ALI for COX-2-derived mediators, in part via enhanced lipoxin signaling, and carry potential therapeutic implications for this devastating clinical disorder.

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Cyclooxygenase‐2 deficient mice are resistant to endotoxin‐induced inflammation and death

Cited by 115 publications

References 49 publications

Contrasting Effects of Cyclooxygenase-1 (COX-1) and COX-2 Deficiency on the Host Response to Influenza A Viral Infection

Contrasting Effects of Cyclooxygenase-1 (COX-1) and COX-2 Deficiency on the Host Response to Influenza A Viral Infection

Simvastatin and a Plant Galactolipid Protect Animals from Septic Shock by Regulating Oxylipin Mediator Dynamics through the MAPK-cPLA2 Signaling Pathway

Cyclooxygenase 2 Plays a Pivotal Role in the Resolution of Acute Lung Injury

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