Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A4

Levy, Bruce D.; Sanctis, George T. De; Devchand, Pallavi R.; Kim, Eugene; Ackerman, Kate G.; Schmidt, Birgitta; Szczeklik, Wojciech; Drazen, Jeffrey M.; Serhan, Charles N.

doi:10.1038/nm748

Cited by 340 publications

(306 citation statements)

References 34 publications

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“…Moreover, ATLa potently attenuates airway hyper-reactivity and eosinophilia in murine allergic airway inflammation via multipronged suppression of inflammatory mediators (41). Such findings highlight the anti-inflammatory profile of lipoxins as being distinct from LTB 4 receptor antagonists.…”

Section: Discussionmentioning

confidence: 83%

An Aspirin-Triggered Lipoxin A4 Stable Analog Displays a Unique Topical Anti-Inflammatory Profile

Schottelius¹,

Giesen²,

Asadullah³

et al. 2002

The Journal of Immunology

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Section: Discussionmentioning

confidence: 83%

An Aspirin-Triggered Lipoxin A4 Stable Analog Displays a Unique Topical Anti-Inflammatory Profile

Schottelius¹,

Giesen²,

Asadullah³

et al. 2002

The Journal of Immunology

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“…4k), we next investigated the impact of an LXA 4 analog, 15-epi-lipoxin analog (ATLa), alone or in combination with RvE1 on airway inflammation. This LX stable analog prevents the development of allergic airway responses 24 , but its influence on resolution in this model has not been determined. ATLa significantly decreased BALF leukocyte numbers, measured at protocol day 21, by a similar magnitude as RvE1 (100ng/day) (Fig.…”

Section: Overlapping Yet Distinct Effects Of Rve1 and LXmentioning

confidence: 98%

“…Murine experimental models of asthma involve allergen sensitization and airway challenge 24 . Little information exists on the time course of natural resolution of allergic airway inflammation after discontinuation of allergen airway challenge.…”

Section: Rve1 Impairs Development Of Airway Inflammationmentioning

confidence: 99%

Resolvin E1 regulates interleukin 23, interferon-γ and lipoxin A4 to promote the resolution of allergic airway inflammation

et al. 2008

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Interleukin-23 (IL-23) is integral to the pathogenesis of chronic inflammation. Resolution of acute inflammation is an active process mediated by specific signals and mediators, such as resolvin E1 (RvE1). Here, we provide the first evidence that RvE1, in nanogram quantities, promotes resolution of inflammatory airway responses in part by directly suppressing IL-23 and IL-6 production in the lung. Also contributing to the pro-resolving effects of RvE1 treatment were increased concentrations of interferon-γ in the lungs of RvE1-treated animals. These findings point to a pivotal role of IL-23 and IL-6-which promote survival and differentiation of T H -17 cells-in maintaining inflammation, and uncover an RvE1-initiated resolution program for allergic airway responses.

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“…Many studies have elucidated the role of cysLTs or effects of the cysLT 1 receptor antagonist (LTRA) on lung eosinophilic inflammation or the remodeling of asthma in animal models (10,11) or humans (12)(13)(14). Contrary to the proinflammatory nature of LTs, lipoxin A 4 , another AA metabolite via 5-LO pathway, is an anti-inflammatory mediator (15,16).…”

mentioning

confidence: 99%

A Novel Role of Cysteinyl Leukotrienes to Promote Dendritic Cell Activation in the Antigen-Induced Immune Responses in the Lung

Okunishi

Dohi

Nakagome

et al. 2004

The Journal of Immunology

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Although the critical role of cysteinyl leukotrienes (cysLTs) in the inflammation, especially eosinophilic lung inflammation, in asthma has been well documented, their role in the early stage of Ag-specific immune response has not been completely clarified. In the present study, with a mouse model of asthma and in vitro studies we demonstrated that cysLTs potentiated dendritic cell (DC) functions such as Ag-presenting capacity and cytokine production. The cysLT-1 receptor antagonist (LTRA) strongly suppressed the activation of these DC functions and led to inhibition of subsequent not only Th2, but also Th1, responses in the early stage of immune response. Moreover, treatment with LTRA during the early stage of the immune response potently suppressed the development of Ag inhalation-induced eosinophilic airway inflammation, mucus production, and airway hyper-reactivity in vivo. Treatment with LTRA significantly increased PGE2 production in the lung, and treatment with the cyclooxygenase inhibitor indomethacin abolished LTRA’s suppressive effect on DCs and deteriorated the Th2 and Th1 responses and airway inflammation. With in vitro studies, we also confirmed that cysLTs production by DCs increased with LPS stimulation, and that LTRA directly suppressed the alloantigen-presenting capacity of DCs. These results suggested that cysLTs potentiate DC functions both in vivo and in vitro, and that LTRA could be beneficial to suppress the initial immune response in many immune-mediated disorders beyond asthma.

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Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A4

Cited by 340 publications

References 34 publications

An Aspirin-Triggered Lipoxin A4 Stable Analog Displays a Unique Topical Anti-Inflammatory Profile

An Aspirin-Triggered Lipoxin A4 Stable Analog Displays a Unique Topical Anti-Inflammatory Profile

Resolvin E1 regulates interleukin 23, interferon-γ and lipoxin A4 to promote the resolution of allergic airway inflammation

A Novel Role of Cysteinyl Leukotrienes to Promote Dendritic Cell Activation in the Antigen-Induced Immune Responses in the Lung

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